Vitamin A deficiency is prevalent in developing nations but rare in developed countries. Less than 1 percent of the American population was deficient in 2013. Some experts believe vitamin A toxicity from synthetic supplements is more common in the United States than deficiency.

A prolonged vitamin deficiency within the diet causes primary vitamin A deficiency. Secondary vitamin A deficiency can result from reduced bioavailability of provitamin A carotenoids (a particular food’s normally absorbable fractions of vitamin A) or from interference with the normal absorption, storage, or transport of vitamin A. Medical conditions such as celiac disease, cystic fibrosis, pancreatic insufficiency, duodenal bypass, chronic diarrhea, bile duct obstruction, and cirrhosis may lead to interference with the absorption or storage of the vitamin. Prolonged protein-energy undernutrition can also contribute to deficiency due to both dietary insufficiency and impaired vitamin A storage and transport. Zinc deficiency in alcoholics may also result in secondary vitamin A deficiency.

Limited research indicates genetic variability in the conversion rates of beta carotene into vitamin A. Specific variations (polymorphisms) in the BCMO1 gene have been identified, which can reduce the activity of the BCMO1 enzyme in humans.

Mild deficiency symptoms include fatigue, vulnerability to infections, and reproductive challenges. More notable vitamin A deficiency signs and symptoms include:

• Night blindness: Night blindness is often the initial indication of vitamin A deficiency. Since vitamin A plays a critical role in regenerating visual pigment, insufficient levels can result in night blindness due to impaired regeneration of visual pigment in retinal rods.
• Conjunctival xerosis: This is the dryness of conjunctiva, the clear, thin membrane that protects our eyes.
• Corneal xerosis (corneal dryness).
• Bitot’s spots: Bitot’s spots are irregular and foamy patches formed by the buildup of keratin on the white of the eyes. They typically manifest in children between the ages of 3 and 6.
• Keratomalacia: Keratomalacia occurs when the cornea becomes ulcerated and begins to liquefy. It is one of the most severe signs of deficiency and has the potential to penetrate and destroy the cornea within days. It also portends to the death of children in developing countries, with 50 percent dying within a year of losing their vision.
• Retinopathy: Retinopathy refers to a group of disorders affecting the retina. It’s the leading cause of preventable blindness.
• Dry skin or hair.

Complications

The complications of vitamin A deficiency include:

• Xerophthalmia, the collection of signs and symptoms of vitamin A deficiency related to the eyes (listed above).
• Poor immunity: The lack of vitamin A generally leads to impaired immunity.
• Stunted growth.
• Thickened organ linings: The linings of the lungs, intestines, and urinary tract become thicker and less flexible.
• Anemia.
• Higher risk of respiratory illness.
• Permanent vision loss or blindness: Many symptoms of vitamin A deficiency can lead to blindness.
• Infertility.
• Death: Over 50 percent of children experiencing severe vitamin A deficiency may not survive.

When we consume foods with vitamin A (in the form of retinyl esters, a combination of fatty acid and retinol), our body absorbs it mainly in the small intestine, where these retinyl esters are broken down into retinol. A small part of the vitamin A we consume is also converted into retinoic acid in the cells of the small intestine.

We also consume foods with carotenoids, such as orange and yellow vegetables and fruits. After being absorbed, some carotenoids are converted into vitamin A (retinaldehyde) in different organs and tissues.

Vitamin A is essential for the following functions:

• Vision health: The retina has two types of light-sensitive cells called rods and cones. When light particles enter the lens, rods and cones turn them into electric signals for the brain to understand. In low-light conditions, retinaldehyde (vitamin A compound) permeates rod cells, where it combines with a protein to make a visual pigment. Light hitting it triggers a reaction, leading to an electric signal that travels to the brain through the optic nerve, creating the sensation of sight. After doing its job, the retinaldehyde converts back into retinol to start the process again. Similar cycles occur with cone cells, which help us see different colors. Vitamin A is crucial for this entire process, as well as for eye development.
• Cellular differentiation: Vitamin A is essential for normal cell differentiation—which occurs during cell renewal—especially in tissues such as the skin and mucous membranes. Vitamin A also has widespread effects on metabolism, interacting with hormones such as thyroid, insulin, and corticosteroids. This interaction is especially important for wound healing, as it boosts the growth and reproduction of skin cells, blood vessels, and collagen.
• Gene regulation: In our cells, vitamin A takes different forms, such as retinoic acid. This acid acts like a hormone, affecting gene expression and various body processes. The active forms of vitamin A bind to specific proteins, which act as on-off switches for genes. These switches can pair up or mix and match, regulating gene activity. Vitamin A can also interact with other hormones, including vitamin D and steroids, thus influencing a broad range of genes. Vitamin A’s involvement in cellular processes affects over 500 genes. It’s also linked to insulin resistance and has implications for lipid metabolism and heat production in fat tissue.
• Reproduction function: Retinoic acid is critical for the proper development of embryos and plays a key role in shaping their limbs, hearts, eyes, and ears. Imbalances in vitamin A levels, both excessive and deficient, are recognized for their potential to induce birth defects.
• Immunity: Vitamin A, initially termed “an anti-infective agent,” is vital for the proper functioning of the immune system. The skin and mucosal cells, whose epithelial regeneration and health maintenance require vitamin A, act as a protective barrier in airways and digestive and urinary tracts and constitute the body’s first defense (innate immunity) against infections. Also, vitamin A is essential for adaptive immunity, influencing helper T-cell and B-cell development, and supporting immune cell function.
• Antioxidant activity: Vitamin A acts as an antioxidant, reducing harm caused by free radicals to DNA.

Vitamin A Prevents Certain Conditions

There is some evidence that vitamin A can help prevent the following conditions:

• Age-related macular degeneration (AMD): AMD is a prevalent, painless eye condition affecting central vision, leading to vision loss in individuals aged 50 and older. Although its exact cause is uncertain, oxidative stress is thought to contribute. Individuals who smoke or have inadequate diets, lacking in fruits and vegetables, face an increased risk of developing AMD. In one study involving over 2,500 participants aged 55 to 80, those using antioxidants (vitamins A and E and beta carotene) and zinc had approximately a 34 percent lower risk of developing advanced AMD than those who received a placebo.
• Cancer: Vitamin A and carotenoids have been shown to control the multiplication, development, and specialization of tumor cells. Research has also found that vitamin A and carotenoids can help prevent various long-term health issues and tumor development. However, the effectiveness of vitamin A in lowering cancer risk remains unclear. Individuals maintaining a healthy diet rich in vitamin A, beta carotene, or other carotenoids appear to experience a reduced risk of specific cancers, including pancreatic, breast, ovarian, colorectal, esophageal, cervical, and melanoma.
• Cognitive decline: One study of 604 participants discovered that individuals at risk for cognitive decline with higher blood levels of alpha carotene, a type of vitamin A containing lutein and zeaxanthin, demonstrated better cognition, including memory, learning, and attention.
• Measles: Measles predominantly affects young children in low-income countries, and vitamin A insufficiency is a significant risk factor for severe measles. The World Health Organization (WHO) suggests administering substantial oral doses of vitamin A to children in regions with high vitamin A deficiency prevalence to reduce illness and mortality, including from measles. However, vitamin A does not seem beneficial unless a child has a deficiency. Not administering vitamin A supplements to a child without proper medical supervision is crucial.

Conditions Vitamin A Can Treat

Prescription creams and pills containing retinoids treat severe acne, psoriasis, skin disorders, warts, and sun-induced premature aging. Research suggests that topical retinoids, combined with antioxidants, may reduce the visibility of fine lines and wrinkles. However, some of these medications have side effects. Notably, pregnant women or women who might become pregnant must avoid isotretinoin, an oral medication for severe acne, to prevent birth defects in the baby.

Bone marrow produces various blood cells essential for the immune system. When the process goes awry due to genetic changes, it can lead to a specific type of leukemia called acute promyelocytic leukemia (APL). The disease creates a fusion protein that disrupts normal cell development and hampers the effects of vitamin A (retinoic acid), thus negatively affecting cell differentiation. High doses of vitamin A treatments can sometimes help restore normal cell differentiation and improve the condition in APL patients.

The vitamin A in our diet comes from the following two forms:

• Preformed vitamin A: Preformed vitamin A is found in animal products such as dairy, eggs, fish, and organ meats. There are two types of preformed vitamin A, including retinol and retinyl esters. In its preformed state, retinol is a biologically active form of vitamin A and is the primary circulating form in the bloodstream. Retinyl esters, such as those of palmitic, oleic, stearic, and linoleic acids, are the main forms of vitamin A storage in the body.
• Provitamin A carotenoids: Provitamin A carotenoids are found in plant pigments such as beta and alpha carotene. The body converts them into vitamin A with the help of an enzyme in the intestine. Other carotenoids such as lycopene, lutein, and zeaxanthin don’t convert into vitamin A and are known as non-provitamin A carotenoids. They potentially have other important functions unrelated to vitamin A.

In addition to retinol, the other two active forms of vitamin A are:

• Retinaldehyde: Within various tissues, retinol is transformed into retinaldehyde through oxidation. The eye needs 11-cis-retinaldehyde, a type of retinaldehyde, to turn light into signals the brain can understand for vision.
• Retinoic acid: Retinol is converted into retinoic acid through oxidation. Retinoic acid plays a vital role in maintaining the normal structure of the cornea and conjunctival membranes, thus preventing xerophthalmia and ensuring proper functioning of the rod and cone cells in the retina.

Retinol, retinaldehyde, retinoic acid, and similar compounds are collectively referred to as retinoids.

In the United States, according to the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine, the recommended dietary allowances (RDAs) for vitamin A are expressed as retinol activity equivalents (RAE) to consider the varied bioactivities of retinol and provitamin A carotenoids, which will also be transformed into retinol. For instance, 1 microgram of RAE equals one of the following:

• 1 microgram of retinol
• 2 micrograms of supplemental beta carotene
• 12 micrograms of dietary beta carotene
• 24 micrograms of dietary alpha carotene or beta cryptoxanthin

Since there’s insufficient evidence to develop RDAs for infants under 1, adequate intakes (AIs) are used instead.

New methods using stable isotope methodologies and isotopic tracer studies have allowed scientists to calculate vitamin A requirements more accurately than before and better estimate how much of the vitamin is required for healthy living. In addition, rat models have highlighted the importance of studying children directly to understand their vitamin A needs rather than relying solely on data from adults. Therefore, it is probably time to review and redefine the RDA values for pregnancy, breastfeeding, and infancy.

Types of vitamin A supplements include:

• Retinol supplements.
• Beta-carotene supplements: Unlike vitamin A, beta carotene doesn’t accumulate in the body, but high doses may still pose risks. Beta-carotene supplements have been linked to an increased risk of lung cancer and death in male smokers or men who used to smoke. However, this link was not found in dietary sources.
• A combination of retinol and beta-carotene supplements.
• Retinyl palmitate and retinyl-acetate supplements: The primary preformed vitamin A forms found in supplements include retinyl palmitate and retinyl acetate, synthetic forms of vitamin A.
• Multivitamins: Most multivitamins contain the RDA for vitamin A. They may contain beta carotene or one of the synthetic forms of vitamin A. If a supplement contains beta carotene as part of its vitamin A content, this detail is specified on the Supplement Facts label under vitamin A.

Vitamin A supplements are available in tablets and capsules and in many dosages, which can vary significantly. A typical amount is 3,000 micrograms RAE, which is also the tolerable upper intake level (UL) in adults.

Precautions

Certain multivitamin supplements in the United States may offer up to 5,000 international units (IU) of preformed vitamin A, equivalent to 1,500 micrograms RAE. This exceeds the current RDA for vitamin A, as the daily values used by the U.S. Food and Drug Administration (FDA) for supplement labeling are based on the 1968 RDA rather than the current one.

Taking cod liver oil for vitamin D may inadvertently lead to excessive vitamin A intake, as it contains high levels of retinyl palmitate. Therefore, it’s crucial to be aware of the vitamin A content in cod liver oil and ensure other supplements do not contribute to additional vitamin A intake. Other fish oils generally do not contain substantial amounts of vitamin A.

In the United States and other high-income countries, 65 percent to 80 percent of vitamin A intake comes from dietary preformed sources. In contrast, with more plant-based diets, low-income countries rely more on provitamin A. The absorption of preformed vitamin A is quite efficient, ranging from 70 percent to 90 percent. The body typically absorbs 10 percent to 30 percent of beta carotene, one type of provitamin A, from foods, and cooking or heat treatment can enhance the bioavailability of beta carotene.

Vitamin A is also commonly added to foods such as milk, and some ready-to-eat cereals. Such foods enriched or fortified with vitamin A contribute 34 percent to 40 percent of vitamin A intake among American children and adolescents. Some foods containing a mixture of ingredients from animal and plant sources have both preformed and provitamin A.

Examples of foods containing vitamin A include:

• Beef liver: pan-fried (6,582 micrograms RAE per 3 ounces)
• Sweet potato: baked in skin (1,403 micrograms RAE each)
• Spinach: frozen, boiled (1,146 micrograms RAE per cup)
• Carrot: raw (918 micrograms RAE per cup)
• Pumpkin pie: store-bought (488 micrograms RAE per piece)
• Ice cream: soft-serve French vanilla (278 micrograms RAE per cup)
• Cantaloupe: raw (270 micrograms RAE per cup)
• Cheese: part-skim ricotta (266 micrograms RAE per cup)
• Sweet pepper: raw, red (234 micrograms RAE per cup)
• Herring: Atlantic, pickled (219 micrograms RAE per 3 ounces)
• Milk: skim with added vitamin A (149 micrograms RAE per cup)
• Mango: raw (112 micrograms RAE each)
• Egg: large, hard-boiled (75 micrograms RAE each)

Apart from dietary sources and supplements, several alternative methods for obtaining vitamin A are available.

Topical creams containing retinoids can be applied directly to the skin for skin-related concerns, such as acne or aging.

Certain medications also contain synthetic forms of vitamin A, such as isotretinoin (Accutane), which should be strictly avoided during pregnancy.

When diagnosing vitamin A deficiency, doctors must rule out other medical conditions that may result in certain symptoms. For instance, impaired dark adaptation, a symptom of night blindness, can also be caused by zinc deficiency, retinitis pigmentosa, severe near-sightedness, cataracts, and diabetic retinopathy. In addition, pellagra, a vitamin B deficiency, can also lead to Bitot’s spot.

A clinical diagnosis can be confirmed through symptoms, classical exam findings, and specific lab tests. The identification of xerophthalmia is highly indicative of vitamin A deficiency.

The golden standard for assessing total body vitamin A is measuring liver retinol concentration through biopsy. However, due to the associated risks, liver biopsies are not commonly used for routine evaluation of vitamin A levels.

Pregnant or breastfeeding women should not exceed preventive or therapeutic doses of 10,000 units (3,000 RAE) per day to prevent potential harm to the fetus or infant.

High-Risk Populations

The following factors make a person more prone to vitamin A deficiency:

• Developing countries: For instance, in some parts of Asia, rice, which lacks beta carotene, serves as the staple food. As a result, residents in these areas suffer from prolonged dietary deprivation of vitamin A.
• Prematurity: Premature newborns’ underdeveloped gastrointestinal tract hinders efficient vitamin A absorption. Also, they have minimal vitamin A stores, and their rapid developmental phase increases their vitamin A requirements.
• Weaning in resource-poor regions: The mother’s nutritional status influences the concentration of vitamin A in breast milk. In resource-poor areas, breast milk typically provides only the minimum daily requirement for infants, thus preventing the accumulation of liver reserves. Consequently, this leads to increased levels of deficiency shortly after weaning.
• Age: Most vitamin A deficiency cases worldwide are in children under age 5. The effects of vitamin A deficiency tend to be more severe in younger patients.
• Malnourishment during pregnancy: Pregnant women in places with food insecurity face higher risk.
• Certain diseases: People with pancreatic, liver, or intestinal diseases are more at risk.
• Bariatric surgeries: Bariatric surgeries, which aim to impede fat absorption by bypassing the duodenum, can result in inadequate absorption of essential fat-soluble vitamins, including vitamin A.
• Restrictive diets: For instance, people suffering from psychiatric disorders, such as anorexia nervosa, may develop vitamin A deficiency due to restricted food intake.

Vitamin A, being fat-soluble, accumulates mainly in the liver due to its storage ability and may lead to potential excess and toxic levels. Vitamin A toxicity could be more prevalent in the U.S. than deficiency due to people’s excessive intake of preformed vitamin A (retinol) in certain supplements.

There are two types of vitamin A toxicity, including:

• Acute toxicity: Acute vitamin A toxicity in children can occur with accidental doses larger than 100,000 RAE. In adults, in addition to excessive supplement intake, acute toxicity has been reported when individuals consume polar bear or seal livers, which can contain over 1 million RAE.
• Chronic toxicity: Chronic vitamin A toxicity in older children and adults typically arises with prolonged daily doses exceeding 30,000 RAE per day, often due to megavitamin therapy or massive daily doses (50,000 to 120,000 RAE) used for conditions such as nodular acne. High doses of vitamin A can lead to liver toxicity.

Symptoms of vitamin A toxicity, both acute and chronic, may include headache and rash.

Symptoms of acute toxicity include:

• Drowsiness
• Irritability
• Abdominal pain
• Nausea
• Vomiting
• Skin peeling

Symptoms of chronic toxicity include:

• Sparse and coarse hair
• Eyebrow hair loss
• Dry and rough skin
• Dry eyes
• Cracked lips
• Increased pressure in the head
• Overall weakness
• Enlarged liver
• Enlarged spleen
• Excessive bone growth and cortical bone thickening
• Joint pain
• Itching
• Loss of appetite
• Failure to thrive in children
• Fractures in older individuals

Treatment for vitamin A toxicity is to cease vitamin A intake. Full recovery typically takes place afterward. Symptoms and signs of prolonged toxicity usually resolve within one to four weeks. However, birth defects in the fetus of a mother who has consumed excessive doses of vitamin A cannot be reversed.

The FNB sets daily tolerable upper limits (ULs) for preformed vitamin A, applicable to both dietary and supplementary intake. They are the same for both males and females and are as follows:

• Birth to 12 months: 600 micrograms
• 1 to 3 years: 600 micrograms
• 4 to 8 years: 900 micrograms
• 9 to 13 years: 1,700 micrograms
• 14 to 18 years: 2,800 micrograms
• 19 years and older: 3,000 micrograms

The ULs for pregnant and lactating mothers remain the same based on their age.

Unlike preformed vitamin A, beta carotene is nontoxic, even at elevated intake levels. The body converts beta carotene into vitamin A as needed, thus eliminating the need for monitoring intake levels. Consequently, a multivitamin supplement primarily containing beta carotene is generally recommended for a safer approach.

Vitamin A can interact with some medications. Individuals using the following drugs regularly should consult their doctors about their vitamin A status:

• Orlistat: Orlistat, a weight-loss treatment, may reduce the absorption of vitamin A in some patients, leading to low plasma levels. Its manufacturers suggest that individuals using it should take a multivitamin supplement containing vitamin A, beta carotene, and other fat-soluble vitamins.
• Cholesterol-lowering drugs: Cholesterol-lowering medications such as cholestyramine and colestipol, which impair fat absorption, may influence the absorption of fat-soluble vitamins, including vitamin A.
• Retinoid analogs: Retinoid analogs, such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin, should not be combined with single-nutrient vitamin A supplements, as this may increase the risk of toxicity.
• Tetracycline antibiotics: Taking high doses of vitamin A along with certain antibiotics known as tetracyclines, including demeclocycline, minocycline, and tetracycline, may increase the risk of intracranial hypertension, characterized by an elevated pressure of brain fluid.
• Antacids: Combining vitamin A with antacids, medications that help neutralize stomach acid to treat heartburn and indigestion, might be more effective in healing ulcers than using antacids alone.
• Anticoagulants: Long-term use or high doses of vitamin A may increase the risk of bleeding in people on blood-thinning medications, especially warfarin.
• Drugs processed by the liver: High doses of vitamin A, especially in combination with medications metabolized by the liver, including acetaminophen, carbamazepine, isoniazid, and methotrexate, may lead to liver damage or failure.
• Neomycin: Neomycin, an antibiotic, may decrease the absorption of vitamin A, particularly in high doses.
• Alcohol: Long-term alcohol consumption can deplete vitamin A stores in the liver and may contribute to liver damage, such as cirrhosis.

Interactions may occur with the following nutrients:

• Vitamin K: High doses of vitamin A might prohibit the absorption of vitamin K.
• Zinc: Zinc deficiency can impact how the body handles vitamin A in several ways. First, it reduces the production of retinol-binding protein (RBP), essential for transporting vitamin A in the bloodstream and protecting against potential toxicity. Second, zinc deficiency lowers the enzyme activity responsible for releasing stored retinol in the liver. Third, zinc is necessary for the enzyme that converts retinol into retinaldehyde.
• Iron: Vitamin A deficiency often occurs alongside iron deficiency, potentially worsening iron deficiency anemia by affecting iron metabolism. Supplementing with both vitamin A and iron appears to be more effective in reducing anemia than using iron or vitamin A alone. In addition, iron deficiency hampers the release of stored vitamin A and can reduce the absorption and permanent use of vitamin A.
• Carotenoids: When taken together, beta carotene and lutein can influence each other’s absorption. For instance, taking purified beta carotene with lutein reduces the absorption of lutein, but the combination increases the absorption of beta carotene.

In addition to the debate over the optimal dosage of vitamin A and supplementation’s adverse effects, there are also controversies regarding whether daily supplementation is necessary, as the liver stores vitamin A for later use, especially in regions where vitamin A deficiency is not prevalent. Additionally, the effectiveness of vitamin A supplementation in preventing certain diseases, such as different types of cancer, remains a topic of discussion.