Vitamin A – Everything You Wanted to Know About this Vitamin

Vitamin A is the name of a group of fat-soluble retinoids, primarily retinol and retinyl esters. Vitamin A is involved in immune function, cellular communication, growth and development, and male and female reproduction. 

Vitamin A supports cell growth and differentiation, playing a critical role in the normal formation and maintenance of the heart, lungs, eyes, and other organs. 

Vitamin A is also critical for vision as an essential component of rhodopsin, the light-sensitive protein in the retina that responds to light entering the eye, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea.

Types of Vitamin A

The human diet contains two sources for vitamin A: preformed vitamin A (retinol and retinyl esters) and provitamin A carotenoids. Preformed vitamin A is found in foods from animal sources, including dairy products, eggs, fish, and organ meats. Provitamin A carotenoids are plant pigments that include beta-carotene, alpha-carotene, and beta-cryptoxanthin. 

The body converts provitamin A carotenoids into vitamin A in the intestine via the beta-carotene monooxygenase type 1 BCMO1 enzyme, although conversion rates may have genetic variability. Other carotenoids in food, such as lycopene, lutein, and zeaxanthin, are not converted into vitamin A and are referred to as non-provitamin A carotenoids; they might have other important activities not involving vitamin A formation.

The various forms of vitamin A are solubilized into micelles in the intestinal lumen and absorbed by duodenal mucosal cells. Retinyl esters and provitamin A carotenoids are converted to retinol after uptake into the lumen (for retinyl esters) or absorption (for provitamin A carotenoids). Retinol is then oxidized to retinal and retinoic acid, the two main active vitamin A metabolites in the body. Most of the body’s vitamin A is stored in the liver in the form of retinyl esters.

Blood Serum Levels of Vitamin A

Retinol and carotenoid levels are typically measured in plasma or serum because blood samples are easy to collect. However, these levels are not always reliable indicators of vitamin A status because they do not decline until vitamin A levels in the liver and other storage sites are almost depleted and because acute and chronic infections can decrease serum and plasma retinol concentrations. 

Most vitamin A is stored in the liver, so measuring vitamin A levels in the liver is the best way to assess vitamin A adequacy. In clinical studies, specialized research laboratories can measure liver vitamin A reserves indirectly using isotope-dilution or dose-response methods, in which plasma levels of retinol, a tracer surrogate, or both are measured over several days after the administration of vitamin A.

In clinical practice, plasma retinol levels alone can be used to document significant deficiency. A serum or plasma retinol concentration of 20 mcg/dL (0.70 micromoles/L) or less frequently reflects moderate vitamin A deficiency, and a level of 10 mcg/dL (0.35 micromoles/L) or less is considered an indicator of severe vitamin A deficiency.

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 National Academies of Sciences, Engineering, and Medicine. 

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 sex, include the following:

• 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.

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

The units of measurement for vitamin A are now mcg RAE, but International Units (IUs) were previously used. To convert IU to mcg RAE, use the following:

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 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, fish, eggs, and dairy products. Most dietary provitamin A in the U.S. diet comes from leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils. 

Vitamin A is routinely added to some foods, including milk and margarine. Some ready-to-eat cereals are also fortified with vitamin A.

About 65% to 80% of vitamin A consumed in the United States and other high-income countries comes from preformed vitamin A, whereas provitamin A is the main form consumed in low-income countries, where diets include more plant-based foods. Among U.S. children and adolescents, enriched and fortified foods account for 34%–40% of vitamin A intakes from food.

The body might absorb up to 75% to 100% of retinol and, in most cases, 10% to 30% of beta-carotene from foods. Cooking and heat treatment can increase the bioavailability of beta-carotene from foods.

Table 2 lists a variety of foods and their vitamin A content per serving. 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.

Dietary supplements

Vitamin A is available in stand-alone supplements and most multivitamins, often in the form of retinyl acetate, retinyl palmitate, provitamin A beta-carotene, or a combination. 

Amounts of vitamin A in supplements vary widely, but 3,000 mcg RAE (333% of the DV) is common. Multivitamins commonly have somewhat lower amounts, often 750 to 1,050 mcg RAE (83% to 117% of the DV).

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

Vitamin A Deficiency

Frank vitamin A deficiency is rare, however, vitamin A deficiency is still common in many developing countries, often as a result of limited access to foods containing preformed vitamin A from animal-based food sources and to foods containing provitamin A carotenoids because of poverty or traditional diets. 

A pooled analysis of population-based surveys from 138 low-income and middle-income countries found that 29% of children age 6 months to 5 years had vitamin A deficiency in 2013. Deficiency rates were highest in sub-Saharan Africa (48%) and South Asia (44%). In addition, approximately 10% to 20% of pregnant women in low-income countries have vitamin A deficiency.

The most common clinical sign of vitamin A deficiency is xerophthalmia, which develops after plasma retinol has been low and the eye’s vitamin A reserves have become depleted. The first sign is night blindness, or the inability to see in low light or darkness as a result of low rhodopsin levels in the retina. 

Xerophthalmia also affects the cornea and can eventually lead to permanent blindness; vitamin A deficiency is one of the top causes of preventable blindness in children.

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

Another effect of chronic vitamin A deficiency is increased severity and mortality risk of infections (particularly measles and infection-associated diarrhea). 

In 2013, 94,500 children in low-income and middle-income countries died of diarrhea and 11,200 died of measles as a result of vitamin A deficiency. More than 95% of deaths attributable to vitamin A deficiency occurred in sub-Saharan Africa and Asia, where vitamin A deficiency was responsible for 2% of all deaths in children younger than 5 years.

Groups at Risk of Vitamin A Inadequacy

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

Premature infants

Preterm infants have low liver stores of vitamin A at birth, and their plasma concentrations of retinol often remain low throughout the first year of life. Preterm infants with vitamin A deficiency have a higher risk of eye and chronic lung diseases. 

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

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

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

People with cystic fibrosis

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

Individuals with gastrointestinal disorders

Approximately one-quarter of children with Crohn’s disease and ulcerative colitis have vitamin A deficiency; adults with these disorders, especially those who have had the disorder for several years, also have a higher risk of vitamin A deficiency. 

Vitamin A and Health

Cancer

Several systematic reviews and meta-analyses of observational studies have shown that higher dietary intakes of retinol, carotenoids, fruits and vegetables, or a combination are associated with a lower risk of lung cancer, non-Hodgkin lymphoma, pancreatic cancer, oral cavity cancer, laryngeal cancer, esophageal cancer, ovarian cancer, glioma, and bladder cancer. 

Age-related macular degeneration

AMD is the leading cause of significant vision loss in older people. AMD’s etiology involves complex interactions among genetic susceptibility, environmental factors (including exposure to oxidative stress), and normal aging. 

Because of the role of oxidative stress in AMD pathophysiology, supplements containing carotenoids with antioxidant functions, such as beta-carotene, lutein, and zeaxanthin, might be useful for preventing or treating this condition. Lutein and zeaxanthin (which are not precursors of vitamin A), in particular, accumulate in the retina, the tissue in the eye that is damaged by AMD.

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

The follow-up AREDS2 study confirmed the value of this supplement in reducing the progression of AMD over a median follow-up period of 5 years. 

Measles

In 2023, measles was responsible for about 107,500 deaths worldwide, mostly in young children in low-income countries. 

A World Health Organization analysis of data from 83 countries showed that 11,200 child deaths from measles were associated with vitamin A deficiency in 2013, and more than 95% of these deaths occurred in sub-Saharan Africa and south Asia.

Research suggests that vitamin A supplementation reduces the risk of measles in children who are at high risk of vitamin A deficiency. However, vitamin A supplementation does not appear to reduce the risk of death from measles. 

A 2022 Cochrane Review included six clinical trials that examined the effect of vitamin A supplementation on the risk of measles in children. These studies enrolled a total of 19,566 children age 6 months to 5 years who lived in low- and middle-income countries. Vitamin A doses ranged from 15,000 mcg RAE (50,000 IU) to 60,000 mcg RAE (200,000 IU), depending on age. Supplements were administered as a single dose or every 4 to 6 months. Vitamin A supplementation reduced the risk of new cases of measles by 50%.