Vitamin A: What you need to know 維生素A：您需要知道的

For consumers

What is vitamin A and what does it do?

Vitamin A is a fat-soluble vitamin that is naturally present in many foods. Vitamin A is important for normal vision, the immune system, and reproduction. Vitamin A also helps the heart, lungs, kidneys, and other organs work properly.

There are two different types of vitamin A. The first type, preformed vitamin A, is found in meat, poultry, fish, and dairy products. The second type, provitamin A, is found in fruits, vegetables, and other plant-based products. The most common type of provitamin A in foods and dietary supplements is beta-carotene.

How much vitamin A do I need?

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

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 boys 14–18 years	900 mcg RAE
Teen girls 14–18 years	700 mcg RAE
Adult men	900 mcg RAE
Adult women	700 mcg RAE
Pregnant teens	750 mcg RAE
Pregnant women	770 mcg RAE
Breastfeeding teens	1,200 mcg RAE
Breastfeeding women	1,300 mcg RAE

What foods provide 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:

• 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.

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. Most multivitamin-mineral supplements contain vitamin A. Dietary supplements that contain only vitamin A are also available.

Am I 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. 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 I 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.

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.

Cancer

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.

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. Among people with AMD who are at high risk of developing advanced AMD, a supplement containing antioxidants, zinc, and copper with or without beta-carotene has shown promise for slowing down the rate of vision loss.

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.

Can vitamin A be harmful?

Yes, high intakes of some forms of vitamin A can be harmful.

Getting too much preformed vitamin A (usually from supplements or certain medicines) can cause dizziness, nausea, headaches, coma, and even death. High intakes of preformed vitamin A in pregnant women can also cause birth defects in their babies. Women who might be pregnant should not take high doses of vitamin A supplements.

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.

The daily upper limits for preformed vitamin A include intakes from all sources—food, beverages, and supplements—and are listed below. These levels do not apply to people who are taking vitamin A for medical reasons under the care of a doctor. Upper limits for beta-carotene and other forms of provitamin A have not been established.

Ages	Upper Limit
Birth to 12 months	600 mcg
Children 1–3 years	600 mcg
Children 4–8 years	900 mcg
Children 9–13 years	1,700 mcg
Teens 14–18 years	2,800 mcg
Adults 19 years and older	3,000 mcg

Does vitamin A interact with medications or other dietary supplements?

Yes, vitamin A supplements can interact or interfere with medicines you take. Here are several examples:

• Orlistat (Alli®, Xenical®), a weight-loss drug, can decrease the absorption of vitamin A, causing low blood levels in some people.
• Several synthetic forms of vitamin A are used in prescription medicines. Examples are the psoriasis treatment acitretin (Soriatane®) and bexarotene (Targretin®), used to treat the skin effects of T-cell lymphoma. Taking these medicines in combination with a vitamin A supplement can cause dangerously high levels of vitamin A in the blood.

Tell your doctor, pharmacist, and other healthcare providers about any dietary supplements and medicines you take. They can tell you if those dietary supplements might interact or interfere with your prescription or over-the-counter medicines or if the medicines might interfere with how your body absorbs, uses, or breaks down nutrients.

Vitamin A and healthful eating

People should get most of their nutrients from food and beverages, according to the federal government’s Dietary Guidelines for Americans. Foods contain vitamins, minerals, dietary fiber and other components that benefit health. In some cases, fortified foods and dietary supplements are useful when it is not possible to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy). For more information about building a healthy dietary pattern, see the Dietary Guidelines for Americans and the U.S. Department of Agriculture’s MyPlate.

Where can I find out more about vitamin A?

• For more information on vitamin A:
  • Office of Dietary Supplements Health Professional Fact Sheet on Vitamin A
  • Vitamin A, MedlinePlus®
• For more information on food sources of vitamin A:
  • U.S. Department of Agriculture’s (USDA’s) FoodData Central
  • Nutrient List for vitamin A (listed by food or by vitamin A content), USDA
  • Nutrient List for beta-carotene (listed by food or by beta-carotene content), USDA
• For more advice on choosing dietary supplements:
  • Office of Dietary Supplements Frequently Asked Questions: Which brand(s) of dietary supplements should I purchase?
• For information about building a healthy dietary pattern:
  • MyPlate
  • Dietary Guidelines for Americans

For professionals

Introduction

Vitamin A is the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters [1-3]. Vitamin A is involved in immune function, vision, reproduction, and cellular communication [1,4,5]. 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 [2-4]. 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 [2].

Two forms of vitamin A are available in the human diet: preformed vitamin A (retinol and its esterified form, retinyl ester) and provitamin A carotenoids [1-5]. Preformed vitamin A is found in foods from animal sources, including dairy products, fish, and meat (especially liver). By far the most important provitamin A carotenoid is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin. 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 [2,3]. 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 [5]. Both retinyl esters and provitamin A carotenoids are converted to retinol, which is oxidized to retinal and then to retinoic acid [2]. 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 [3]. 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 [5]. A plasma retinol level increase of at least 20% indicates an inadequate vitamin A level [3,5,6]. 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 [5]. 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.

Recommended Intakes

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) [5]. 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.

RDAs for vitamin A are given as retinol activity equivalents (RAE) to account for the different bioactivities of retinol and provitamin A carotenoids, all of which are converted by the body into retinol (see Table 1). One mcg RAE is equivalent to 1 mcg retinol, 2 mcg supplemental beta-carotene, 12 mcg dietary beta-carotene, or 24 mcg dietary alpha-carotene or beta-cryptoxanthin [5].

Age	Male	Female	Pregnancy	Lactation
0–6 months*	400 mcg RAE	400 mcg RAE
7–12 months*	500 mcg RAE	500 mcg RAE
1–3 years	300 mcg RAE	300 mcg RAE
4–8 years	400 mcg RAE	400 mcg RAE
9–13 years	600 mcg RAE	600 mcg RAE
14–18 years	900 mcg RAE	700 mcg RAE	750 mcg RAE	1,200 mcg RAE
19–50 years	900 mcg RAE	700 mcg RAE	770 mcg RAE	1,300 mcg RAE
51+ years	900 mcg RAE	700 mcg RAE

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

International Units and mcg RAE

Vitamin A is now measured in mcg RAE, but it was previously measured in International Units (IUs) [7]. To convert IU to mcg RAE, use the following [8]:

• 1 IU retinol = 0.3 mcg RAE
• 1 IU supplemental beta-carotene = 0.3 mcg RAE
• 1 IU dietary beta-carotene = 0.05 mcg RAE
• 1 IU dietary alpha-carotene or beta-cryptoxanthin = 0.025 mcg RAE

RAE can only be directly converted into IUs if the source or sources of vitamin A are known. 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) or if the supplement source is beta-carotene. This RDA is also equivalent to 18,000 IU beta-carotene from food or to 36,000 IU alpha-carotene or beta-cryptoxanthin from food. Therefore, a mixed diet containing 900 mcg RAE provides between 3,000 and 36,000 IU vitamin A, depending on the foods consumed.

Sources of Vitamin A

Food

Concentrations of preformed vitamin A are highest in liver and fish oils [2]. Other sources of preformed vitamin A are milk and eggs, which also include some provitamin A [2]. Most dietary provitamin A comes from leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils [2]. 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 [4,5].

Table 2 suggests many dietary 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.

Food	Micrograms (mcg) RAE per serving	Percent DV*
Beef liver, pan fried, 3 ounces	6,582	731
Sweet potato, baked in skin, 1 whole	1,403	156
Spinach, frozen, boiled, ½ cup	573	64
Pumpkin pie, commercially prepared, 1 piece	488	54
Carrots, raw, ½ cup	459	51
Ice cream, French vanilla, soft serve, 1 cup	278	31
Cheese, ricotta, part skim, 1 cup	263	29
Herring, Atlantic, pickled, 3 ounces	219	24
Milk, fat free or skim, with added vitamin A and vitamin D, 1 cup	149	17
Cantaloupe, raw, ½ cup	135	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, 10 halves	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

*DV = Daily Value. FDA developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for vitamin A is 900 mcg RAE for adults and children age 4 years and older [8], 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. 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 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 [9] lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin A in IUs arranged by nutrient content and by food name, and foods containing beta-carotene in mcg arranged by nutrient content and by food name.

Dietary supplements

Vitamin A is available in multivitamins and as a stand-alone supplement, often in the form of retinyl acetate or retinyl palmitate [2]. 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 [2]. Multivitamin supplements typically contain 750–3,000 mcg RAE (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 [10]. 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.

Vitamin A Intakes and Status

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 RAE [11]. 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.

Data from NHANES III, conducted in 1988–1994, found that approximately 26% of the vitamin A in RAEs consumed by men and 34% of that consumed by women in the United States comes from provitamin A carotenoids, with the remainder coming from preformed vitamin A, mostly in the form of retinyl esters [5].

The adequacy of vitamin A intake decreases with age in children [4]. Furthermore, girls and African-American children have a higher risk of consuming less than two-thirds of the vitamin A RDA than other children [4].

Vitamin A Deficiency

Frank vitamin A deficiency is rare in the United States. 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 [2]. According to the World Health Organization, 190 million preschool-aged children and 19.1 million pregnant women around the world have a serum retinol concentration below 0.70 micromoles/L [12]. 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.

In developing countries, vitamin A deficiency typically begins during infancy, when infants do not receive adequate supplies of colostrum or breast milk [12]. Chronic diarrhea also leads to excessive loss of vitamin A in young children, and vitamin A deficiency increases the risk of diarrhea [5,13]. 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 [2,14]. Vitamin A deficiency is one of the top causes of preventable blindness in children [12]. 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 [3,12]. Vitamin A deficiency also increases the severity and mortality risk of infections (particularly diarrhea and measles) even before the onset of xerophthalmia [5,12,14].

Groups at Risk of Vitamin A Inadequacy

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 [15]. 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 [15,16]. Preterm infants with vitamin A deficiency have an increased risk of eye, chronic lung, and gastrointestinal diseases [15].

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 [17]. The prevalence of vitamin A deficiency in developing countries begins to increase in young children just after they stop breastfeeding [3]. 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 [18]. The World Health Organization estimates that 9.8 million pregnant women around the world have xerophthalmia as a result of vitamin A deficiency [12]. 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 [19,20]. Several cross-sectional studies found that 15%–40% of patients with cystic fibrosis have vitamin A deficiency [21]. However, improved pancreatic replacement treatments, better nutrition, and caloric supplements have helped most patients with cystic fibrosis become vitamin A sufficient [21]. 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 [20-22].

Vitamin A and Health

This section focuses on three diseases and disorders in which vitamin A might play a role: cancer, age-related macular degeneration (AMD), and measles.

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 is unclear.

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 [1,23]. 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 7,500 mcg RAE (25,000 IU) retinyl palmitate for 4 years, on average [24]. 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 [25]. 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 [26]. In all three of these studies, taking very high doses of beta-carotene, with or without 7,500 mcg RAE (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 [27]. However, the ATBC study found that baseline serum beta-carotene and retinol levels and supplemental beta-carotene had no effect on survival [28]. 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 [29].

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) is a major cause of significant vision loss in older people. AMD’s etiology 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 AMD.

The Age-Related Eye Disease Study (AREDS), a large randomized clinical trial, found that participants at high risk of developing advanced AMD (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 (180 mg [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 [30].

A 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 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 [31]. 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 [31]. 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 healthcare provider about taking one of the supplement formulations used in AREDS.

Measles

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 (60,000 mcg RAE [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 [32].

A Cochrane review of eight randomized controlled trials of treatment with vitamin A for children with measles found that 60,000 mcg RAE (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 [32]. 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 30,000 mcg RAE (100,000 IU) in infants and 60,000 mcg RAE (200,000 IU) in older children significantly reduced measles mortality [33]. 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 [34]. 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 [35].

Health Risks from Excessive Vitamin A

Because vitamin A is fat soluble, the body stores excess amounts, primarily in the liver, and these levels can accumulate. Although excess preformed vitamin A can have significant toxicity (known as hypervitaminosis A), large amounts of beta-carotene and other provitamin A carotenoids are not associated with major adverse effects [36]. The manifestations of hypervitaminosis A depend on the size and rapidity of the excess intake. The symptoms of hypervitaminosis A following sudden, massive intakes of vitamin A, as with Arctic explorers who ate polar bear liver, are acute [37]. Chronic intakes of excess vitamin A lead to increased intracranial pressure (pseudotumor cerebri), dizziness, nausea, headaches, skin irritation, pain in joints and bones, coma, and even death [2,4,5]. Although hypervitaminosis A can be due to excessive dietary intakes, the condition is usually a result of consuming too much preformed vitamin A from supplements or therapeutic retinoids [3,5]. When people consume too much vitamin A, their tissue levels take a long time to fall after they discontinue their intake, and the resulting liver damage is not always reversible.

Observational studies have suggested an association between high intakes of preformed vitamin A (more than 1,500 mcg daily—only slightly higher than the RDA), reduced bone mineral density, and increased fracture risk [1,4,38]. However, the results of studies on this risk have been mixed, so the safe retinol intake level for this association is unknown.

Total intakes of preformed vitamin A that exceed the UL and some synthetic retinoids used as topical therapies (such as isotretinoin and etretinate) can cause congenital birth defects [2-4]. These birth defects can include malformations of the eye, skull, lungs, and heart [4]. Women who might be pregnant should not take high doses of vitamin A supplements [2].

Unlike preformed vitamin A, beta-carotene is not known to be teratogenic or lead to reproductive toxicity [1]. And even large supplemental doses (20–30 mg/day) of beta-carotene or diets with high levels of carotenoid-rich food for long periods are not associated with toxicity. The most significant effect of long-term, excess beta-carotene is carotenodermia, a harmless condition in which the skin becomes yellow-orange [1,23]. This condition can be reversed by discontinuing beta-carotene ingestion.

Supplementation with beta-carotene, with or without retinyl palmitate, for 5–8 years has been associated with an increased risk of lung cancer and cardiovascular disease in current and former male and female smokers and in male current and former smokers occupationally exposed to asbestos [25,39]. In the ATBC study, beta-carotene supplements (20 mg daily) were also associated with increased mortality, mainly due to lung cancer and ischemic heart disease [25]. The CARET study ended early, after the investigators found that daily beta-carotene (30 mg) and retinyl palmitate (7,500 mcg RAE [25,000 IU]) supplements increased the risk of lung cancer and cardiovascular disease mortality [39].

The FNB has established ULs for preformed vitamin A that apply to both food and supplement intakes [5]. The FNB based these ULs on the amounts associated with an increased risk of liver abnormalities in men and women, teratogenic effects, and a range of toxic effects in infants and children. The FNB also considered levels of preformed vitamin A associated with decreased bone mineral density, but did not use these data as the basis for its ULs because the evidence was conflicting. The FNB has not established ULs for beta-carotene and other provitamin A carotenoids [23]. The FNB advises against beta-carotene supplements for the general population, except as a provitamin A source to prevent vitamin A deficiency.

Age	Male	Female	Pregnancy	Lactation
0–12 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

* These ULs only apply 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 as retinol or its ester forms. For example, the vitamin A in some supplements consists partly or entirely of beta-carotene or other provitamin A carotenoids. 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.

Interactions with Medications

Vitamin A can interact with certain medications, and some medications can have an adverse effect on vitamin A levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin A status with their healthcare providers.

Orlistat

Orlistat (Alli®, Xenical®), a weight-loss treatment, can decrease the absorption of vitamin A, other fat-soluble vitamins, and beta-carotene, causing low plasma levels in some patients [40]. The manufacturers of Alli and Xenical recommend encouraging patients on orlistat to take a multivitamin supplement containing vitamin A and beta-carotene, as well as other fat-soluble vitamins [41,42].

Retinoids

Several synthetic retinoids derived from vitamin A are used orally as prescription medicines. Examples include the psoriasis treatment acitretin (Soriatane®) and bexarotene (Targretin®), used to treat the skin effects of T-cell lymphoma. Retinoids can increase the risk of hypervitaminosis A when taken in combination with vitamin A supplements [40].

Vitamin A and Healthful Diets

The federal government’s 2020-2025 Dietary Guidelines for Americans notes that “Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods. … In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy).”

For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture’s MyPlate.

The Dietary Guidelines for Americans describes a healthy dietary pattern as one that:

• Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils. Many fruits, vegetables, and dairy products are good sources of vitamin A. Some ready-to-eat breakfast cereals are fortified with vitamin A.
• Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products. Beef liver contains high amounts of vitamin A. Other sources of the nutrient include eggs and some fish.
• Limits foods and beverages higher in added sugars, saturated fat, and sodium.
• Limits alcoholic beverages.
• Stays within your daily calorie needs.

References

1. Johnson EJ, Russell RM. Beta-Carotene. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:115-20.
2. Ross CA. Vitamin A. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:778-91.
3. Ross A. Vitamin A and Carotenoids. In: Shils M, Shike M, Ross A, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006:351-75.
4. Solomons NW. Vitamin A. In: Bowman B, Russell R, eds. Present Knowledge in Nutrition. 9th ed. Washington, DC: International Life Sciences Institute; 2006:157-83.
5. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001.
6. Tanumihardjo SA. Vitamin A: biomarkers of nutrition for development. Am J Clin Nutr 2011;94:658S-65S. [PubMed abstract]
7. U.S. Food and Drug Administration. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. 2016.
8. U.S. Food and Drug Administration. Food Labeling: Revision of the Nutrition and Supplement Facts Labels and Serving Sizes of Foods That Can Reasonably Be Consumed at One Eating Occasion; Dual-Column Labeling; Updating, Modifying, and Establishing Certain Reference Amounts Customarily Consumed; Serving Size for Breath Mints; and Technical Amendments; Proposed Extension of Compliance Dates. 2017.
9. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, 2019.
10. Bailey RL, Gahche JJ, Lentino CV, Dwyer JT, Engel JS, Thomas PR, et al. Dietary supplement use in the United States, 2003-2006. J Nutr 2011;141:261-6. [PubMed abstract]
11. U.S. Department of Agriculture, Agricultural Research Service. What We Eat in America, 2007-2008.
12. World Health Organization. Global Prevalence of Vitamin A Deficiency in Populations at Risk 1995–2005: WHO Global Database on Vitamin A Deficiency. Geneva: World Health Organization; 2009.
13. Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ 2011;343:d5094. [PubMed abstract]
14. Sommer A. Vitamin A deficiency and clinical disease: An historical overview. J Nutr 2008;138:1835-9. [PubMed abstract]
15. Mactier H, Weaver LT. Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Arch Dis Child Fetal Neonatal Ed 2005;90:F103-8. [PubMed abstract]
16. Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev 2007:CD000501. [PubMed abstract]
17. Oliveira-Menegozzo JM, Bergamaschi DP, Middleton P, East CE. Vitamin A supplementation for postpartum women. Cochrane Database Syst Rev 2010:CD005944. [PubMed abstract]
18. van den Broek N, Dou L, Othman M, Neilson JP, Gates S, Gulmezoglu AM. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev 2010:CD008666. [PubMed abstract]
19. Graham-Maar RC, Schall JI, Stettler N, Zemel BS, Stallings VA. Elevated vitamin A intake and serum retinol in preadolescent children with cystic fibrosis. Am J Clin Nutr 2006;84:174-82. [PubMed abstract]
20. O’Neil C, Shevill E, Chang AB. Vitamin A supplementation for cystic fibrosis. Cochrane Database Syst Rev 2010:CD006751.pub2. [PubMed abstract]
21. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 2002;35:246-59.
22. Michel SH, Maqbool A, Hanna MD, Mascarenhas M. Nutrition management of pediatric patients who have cystic fibrosis. Pediatr Clin North Am 2009;56:1123-41. [PubMed abstract]
23. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000.
24. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5. [PubMed abstract]
25. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-35. [PubMed abstract]
26. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. The New England journal of medicine 1996;334:1145-9. [PubMed abstract]
27. Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King IB, Thornquist M, et al. Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev 2009;18:2202-6. [PubMed abstract]
28. Watters JL, Gail MH, Weinstein SJ, Virtamo J, Albanes D. Associations between alpha-tocopherol, beta-carotene, and retinol and prostate cancer survival. Cancer Res 2009;69:3833-41. [PubMed abstract]
29. Mondul AM, Watters JL, Mannisto S, Weinstein SJ, Snyder K, Virtamo J, et al. Serum retinol and risk of prostate cancer. Am J Epidemiol 2011;173:813-21. [PubMed abstract]
30. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36. [PubMed abstract]
31. The Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;309:2005-15. [PubMed abstract]
32. Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. Cochrane Database Syst Rev 2011;2005.
33. Sudfeld CR, Navar AM, Halsey NA. Effectiveness of measles vaccination and vitamin A treatment. Int J Epidemiol 2010;39 Suppl 1:i48-55. [PubMed abstract]
34. Bello S, Meremikwu MM, Ejemot-Nwadiaro RI, Oduwole O. Routine vitamin A supplementation for the prevention of blindness due to measles infection in children. Cochrane Database Syst Rev 2011:CD007719. [PubMed abstract]
35. Foster A, Sommer A. Corneal ulceration, measles, and childhood blindness in Tanzania. Br J Ophthalmol 1987;71:331-43. [PubMed abstract]
36. Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, et al. Beta-carotene is an important vitamin A source for humans. The Journal of Nutrition 2010;140:2268S-85S. [PubMed abstract]
37. Rodahl K, Moore T. The vitamin A content and toxicity of bear and seal liver. Biochem J 1943;37:166-8. [PubMed abstract]
38. Ribaya-Mercado JD, Blumberg JB. Vitamin A: is it a risk factor for osteoporosis and bone fracture? Nutr Rev 2007;65:425-38. [PubMed abstract]
39. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL, Omenn GS, et al. The beta-carotene and retinol efficacy trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping β-carotene and retinol supplements. J Natl Cancer Inst 2004;96:1743-50. [PubMed abstract]
40. Natural Medicines Comprehensive Database. Vitamin A. 2011.
41. Genentech USA, Inc. Xenical Package Insert. 2010.
42. GlaxoSmithKline. Alli: Potential for Misuse and Drug Interactions. 2011.

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