Vitamin A: Functions, Deficiency, and Overdose

Vitamin A is not a single substance, but a whole group of fat-soluble compounds collectively known as retinoids. These include retinol, retinal, and retinyl esters, as well as certain plant-based carotenoids, which are converted into the active form of vitamin A in the body. Vitamin A is essential for vision, normal growth and development, immune system function, and the maintenance of the integrity of the skin and mucous membranes. [1]

Unlike water-soluble vitamins, vitamin A can accumulate in the liver and adipose tissue. This is beneficial, as the body creates reserves in case of temporary nutritional deficiencies. However, long-term excess retinol from supplements and certain foods can lead to toxic effects, especially when taken in large doses. Therefore, it's important to maintain a balance between vitamin A deficiency and excess. [2]

The body receives vitamin A in two main forms. The first is ready-made retinol and retinyl esters from animal products and supplements. The second is provitamin A carotenoids, primarily beta carotene, which are found in fruits and vegetables and can be partially converted into retinol. These forms differ in bioavailability and safety: excess carotenoids generally do not cause toxicity, whereas an excess of ready-made retinol can be dangerous. [3]

Vitamin A is especially important during childhood, when tissue growth is active and the immune system is developing. In regions with nutritional deficiencies, vitamin A deficiency causes night blindness, corneal damage, and increased mortality from infections in children. Meanwhile, in countries with widespread use of supplements and fortified foods, the problem of hidden retinol excess in adults is more commonly discussed. [4]

For adults, the optimal strategy is to obtain vitamin A primarily from food, combining animal products with carotenoid-rich fruits and vegetables. Supplements make sense in cases of proven deficiency or in specific clinical situations, but not as a universal remedy for "improving vision" or "rejuvenating skin." [5]

Table 1. Quick facts about vitamin A

Parameter	Characteristic
Group of substances	Retinol, retinal, retinyl esters, provitamin A carotenoids
Solubility	Fat-soluble vitamin
Main functions	Vision, immunity, growth and development, skin and mucous membrane condition
Main depot	Liver
The danger of excess	Hypervitaminosis is possible with chronic excess of retinol.
Main food sources	Liver, eggs, fatty fish, dairy products, brightly colored vegetables and fruits

Forms of vitamin A and metabolic features

The name "vitamin A" covers several forms. "Preformed" vitamin A is retinol and its esters (most commonly retinyl palmitate), which are found in animal products and most vitamin A supplements. These compounds are easily absorbed and quickly increase retinol levels in the blood, but they are associated with the risk of toxicity when taken in excess. [6]

Provitamin A carotenoids, such as beta carotene, alpha carotene, and beta cryptoxanthin, are obtained primarily from plant foods. In the intestine, some of these pigments are converted to retinal and then to retinol, but conversion is far from complete and depends on intestinal health, dietary composition, and genetic factors. This makes carotenoids a more "self-regulating" source of vitamin A: with sufficient supply, conversion is reduced. [7]

Retinol is absorbed in the small intestine along with fats. This requires bile acids and normal pancreatic function. Within enterocytes, retinol is esterified and incorporated into chylomicrons, which are carried via the lymphatic system into the blood and then to the liver. The liver accumulates most of the ingested vitamin A as retinyl esters, creating a depot that can last several months in an adult.

When the body needs vitamin A, the liver releases retinol and binds it to a special retinol-binding protein. This complex is transported into the blood, delivering the vitamin to organs and tissues. In the retina, some retinol is converted to retinal and incorporated into the visual pigment rhodopsin. In other tissues, retinal is further oxidized to retinoic acid, which acts as a signaling molecule and regulates gene expression. [8]

Vitamin A is excreted slowly, primarily in bile and partially in urine as metabolites. Because of this, prolonged use of high doses of retinol can lead to gradual accumulation and the development of chronic hypervitaminosis. In contrast, excessive carotenoid intake often manifests only as skin discoloration (carotenoderma) without toxic damage to the liver or bones. [9]

Table 2. The main forms of vitamin A and their characteristics

Form	Source	Advantages	Potential risks
Retinol, retinyl esters	Animal products, additives	High bioavailability	Risk of toxicity if taken in excess
Beta carotene	Orange and dark green vegetables and fruits	Additional antioxidant effect	In case of excess, only carotenoderma is possible.
Other carotenoids	Leafy vegetables, some fruits	Contribution to the total provitamin A pool	Less studied conversion to retinol

Biological functions of vitamin A

One of the most well-known functions of vitamin A is its role in vision. In the retina, retinal binds to the protein opsin to form rhodopsin, which can detect even weak light. Vitamin A deficiency reduces rhodopsin levels, impairs dark adaptation, and leads to night blindness. Prolonged and severe deficiency damages the cornea and conjunctiva, which can lead to irreversible vision loss. [10]

Vitamin A plays an equally important role in maintaining epithelial integrity. Retinoids regulate the growth and differentiation of epithelial cells in the skin, respiratory tract, genitourinary system, and gastrointestinal tract. A vitamin A deficiency causes mucous membranes to thin, mucus production to decrease, and barrier function to be impaired, increasing the risk of infections and chronic inflammation.

Vitamin A plays a role in the immune system. It influences the maturation and function of T and B lymphocytes, supports the activity of natural killer cells, and is involved in antibody production. Vitamin A deficiency makes the body less able to fight viral and bacterial infections, especially in childhood. This is why preventative vitamin A supplementation programs for children in malnourished regions have been shown to reduce mortality from infectious diseases. [11]

Retinoids play a key role in growth and development. They regulate the expression of numerous genes responsible for the formation of organs and tissues, including the heart, lungs, bones, and the reproductive system. Adults need vitamin A for skin cell renewal, spermatogenesis, and the normal functioning of the placenta and fetus during pregnancy. Both vitamin A deficiency and excess are equally dangerous for embryonic development, so it is especially important for pregnant women to adhere to recommended levels. [12]

Vitamin A is considered an antioxidant, although this role is more often attributed to its provitamin beta-carotene. Carotenoids can neutralize certain free radicals and protect cell membrane lipids from peroxidation. However, in high doses, retinol itself can exhibit pro-oxidant properties, further emphasizing the importance of moderation.

Table 3. Main functions of vitamin A by body systems

System	The role of vitamin A
Visual	Rhodopsin formation, dark adaptation, corneal protection
Immune	Lymphocyte maturation, antibody production, anti-infective protection
Epithelial	Maintaining the integrity of the skin and mucous membranes
Reproductive	Spermatogenesis, normal pregnancy and fetal development
Bone and connective tissue	Formation of bone tissue, cartilage and other structures

Sources of vitamin A and daily requirement

Preformed vitamin A (retinol and retinyl esters) is found primarily in animal products. It is especially rich in liver and liver products, fatty fish, butter, cream, whole milk, cheese, and eggs. When regularly consuming liver, it is important to be aware of the risk of excess vitamin A, especially in pregnant women, who are advised to limit such foods. [13]

Provitamin A carotenoids are found in plant foods. Beta-carotene is abundant in carrots, pumpkin, sweet peppers, spinach, broccoli, apricots, and other brightly colored vegetables and fruits. Carotenoids are better absorbed from cooked and chopped foods in the presence of fat, so stews, purees, and vegetables with vegetable oil may be a more effective source of provitamin A than raw vegetables without added fat. [14]

The retinol equivalent (RE) is used to estimate vitamin A intake. Recommendations take into account both the available retinol and the portion of carotenoids capable of converting into vitamin A. European recommendations set the estimated daily requirement for adult men at approximately 750 micrograms of retinol equivalents, and for women, approximately 650 micrograms. For children and adolescents, the norms are lower and vary with age, while for pregnant and lactating women, the requirement is somewhat higher. [15]

With a typical diet including meat, dairy, eggs, and vegetables, most adults achieve these levels without supplements. Vegetarians and especially vegans should ensure they get sufficient carotenoid intake from a variety of fruits and vegetables, and if you have any concerns about your intake, it's a good idea to discuss your diet with a specialist. It's important to note that plant carotenoids are not completely converted to retinol, so relying on just one food (such as carrots) may not be sufficient. [16]

Many vitamin and mineral supplements contain vitamin A as retinyl palmitate or retinyl acetate, sometimes combined with beta carotene. When choosing a supplement, it's important to consider your total vitamin A intake from all sources to avoid exceeding the tolerable upper limit, especially with long-term use. [17]

Table 4. Foods rich in vitamin A

Product	Basic form	Vitamin A content assessment*
Beef or cod liver	Retinol, retinyl esters	Very high, easily covers the daily requirement
Egg yolk	Retinol	Average, significant contribution to the diet
Fatty fish	Retinol	Average
Milk, cream, cheese	Retinol	Low or medium, depending on fat content
Carrots, pumpkin	Beta carotene	High in carotenoids
Spinach, broccoli	Carotenoids	Average

* Values depend on variety, growing conditions and preparation. [18]

Table 5. Estimated daily requirements for vitamin A

Group	Estimated daily requirement, micrograms of retinol equivalents
Children 1-3 years old	250-300
Children 4-8 years old	350-400
Teenagers 9-13 years old	400-600
Teenagers 14-18 years old	600-700
Adult men	About 750
Adult women	About 650
Pregnant and lactating women	70-100 above the age norm

[19]

Vitamin A deficiency: manifestations and consequences

Vitamin A deficiency remains a key nutritional problem in some regions of the world due to its prevalence and severity. Deficiency reduces the concentration of retinol and its derivatives in the blood and tissues, and depletes liver stores. Initially, night vision is impaired, followed by changes in the conjunctiva and cornea. Severe and prolonged deficiency leads to xerophthalmia and irreversible blindness. [20]

In addition to the eyes, the skin and mucous membranes are affected. Dry skin, a tendency to peel, cracks, and hyperkeratosis appear. The mucous membranes of the respiratory tract, intestines, and genitourinary system lose their normal protective properties, leading to frequent infections, chronic inflammation, and worsening of existing conditions.

In childhood, vitamin A deficiency is particularly dangerous. It slows growth, impairs immune system development, and increases the risk of severe and fatal outcomes from measles, diarrhea, and other infections. Large meta-analyses show that in regions with severe vitamin A deficiency, prophylactic high-dose courses in children aged 6 months to 5 years reduce overall mortality and the incidence of complications. [21]

In adults, vitamin A deficiency often has subtle symptoms: decreased adaptation to darkness, dry skin, brittle hair and nails, and increased susceptibility to colds. It can be associated with deficiencies of other micronutrients, especially iron and zinc, and is often found in people with chronic intestinal and liver diseases that impair the absorption and metabolism of fat-soluble vitamins. [22]

Deficiency diagnosis is based on a combination of clinical presentation and laboratory parameters. Serum retinol levels are an important marker: values below approximately 0.7 micromoles per liter are generally interpreted as subclinical deficiency, while values below 0.35 micromoles per liter are considered severe deficiency. The presence of inflammation, which itself can reduce retinol levels, is also taken into account when interpreting test results. [23]

Table 6. Main manifestations of vitamin A deficiency

Degree of deficiency	Typical signs
Early manifestations	Decreased adaptation to darkness, dry skin, brittle hair
Mild insufficiency	Frequent colds, dry mucous membranes, mild dermatological changes
Moderate deficiency	Night blindness, conjunctival xerosis, dry and cracked skin
Severe deficit	Xerophthalmia, corneal damage, high risk of blindness
Deficiency due to diseases	Combination with malabsorption, anemia, and other micronutrient deficiencies

Excess Vitamin A and Safety

Since vitamin A is fat-soluble and accumulates in the liver and adipose tissue, chronic excess can lead to toxic damage to the body. Acute hypervitaminosis occurs when very high doses are taken over a short period and is characterized by nausea, vomiting, headache, dizziness, and impaired coordination. Chronic overdose develops gradually with regular exceedance of recommended doses and is dangerous due to liver and bone damage. [24]

In adults, the tolerable upper intake level for vitamin A is generally set at approximately 3,000 micrograms of retinol equivalents per day, taking into account the total intake from food and supplements. Exceeding these levels over a long period increases the risk of toxicity, especially in people with liver disease, alcohol dependence, or lipid metabolism disorders. [25]

Chronic hypervitaminosis can manifest as dry skin, hair loss, brittle nails, bone and joint pain, liver enlargement, elevated liver enzymes, and visual impairment. Some patients have reported an increased risk of osteoporosis and fractures with long-term use of high doses of retinol. Symptoms often mimic other medical conditions, so it is important to consider the supplement history and diet. [26]

Pregnant women are particularly vulnerable. Excessive retinol intake in the first trimester is associated with an increased risk of congenital malformations. Therefore, pregnant women are advised against high therapeutic doses of vitamin A, as well as frequent use of liver and medicinal retinoids without strict indications and specialist supervision. Provitamin A carotenoids are safer in this regard and are not associated with a teratogenic risk. [27]

In typical prophylactic doses close to the daily requirement, vitamin A is well tolerated, and excess retinol from regular food rarely leads to toxicity, unless overused in the liver or with concentrated preparations. The problem of excess occurs much more often with the uncontrolled use of vitamin A mono-preparations and high-dose multivitamins. [28]

Table 7. Vitamin A intake ranges and expected risk

Consumption level	Risk assessment
Within the daily requirement	Optimal, maintains normal functions
Up to the upper permissible level	Generally safe in the absence of liver disease
Long-term excess of the upper level	Risk of chronic hypervitaminosis
Single administration of very high doses	Risk of acute hypervitaminosis
High doses during pregnancy	Risk of teratogenic effects

Vitamin A Supplements: When You Really Need Them

The primary purpose of vitamin A supplements is to treat and prevent deficiency in high-risk groups. In countries and regions where severe vitamin A deficiency is common among children, mass prevention programs using periodic high-dose retinol in children aged 6 months to 5 years have proven effective in reducing mortality and the incidence of severe infections. Such programs are implemented according to the standards of international organizations and should not be extended to less vulnerable regions unless necessary. [29]

In adults, vitamin A supplements may be prescribed for conditions that impair the absorption of fats and fat-soluble vitamins, such as chronic bowel disease, small bowel resections, or severe liver and pancreatic disease. In these cases, the dosage and duration of treatment are determined by a physician based on test results and concomitant therapy. [30]

In dermatology and ophthalmology, synthetic retinoids are used. They are derivatives of vitamin A and have a pronounced effect on cell division and keratin synthesis. These drugs are used for severe forms of acne, psoriasis, and certain hereditary corneal diseases. However, these medications have potentially serious side effects, including teratogenicity, and are not related to self-administered vitamin supplements. [31]

For healthy adults living in adequately nourished environments, routine high-dose vitamin A supplementation for the purpose of "improving vision," "boosting immunity," or "rejuvenating skin" lacks compelling evidence and carries the risk of hidden retinol accumulation in the liver. In most cases, a balanced diet and, when necessary, moderate doses in standard multivitamin supplements not exceeding the daily requirement are sufficient. [32]

Combinations of beta carotene with other antioxidants deserve special mention. Early studies suggested that such combinations could reduce the risk of cardiovascular disease and certain types of cancer. However, later, larger studies have shown that high doses of beta carotene in smokers are associated with an increased risk of lung cancer. Therefore, even relatively "mild" forms of vitamin A in the form of carotenoids should not be used in high doses without justification. [33]

Table 8. Situations when vitamin A supplementation is justified

Situation	Comment
Confirmed deficiency in children	Treatment and prevention according to schemes approved by health organizations
Deficiency in adults	Prescription based on laboratory data and diet
Diseases with impaired fat absorption	Combination therapy under the supervision of a physician
Prevention programs in regions with shortages	Standardized courses to reduce mortality
Short-term use as part of a multivitamin	In moderate doses in case of malnutrition

Practical findings and conclusion

Vitamin A is a vital fat-soluble vitamin with a broad spectrum of activity. It is necessary for normal vision, immune system function, growth and development, and maintaining the integrity of the skin and mucous membranes. Vitamin A deficiency is particularly dangerous for children and leads to increased mortality from infections and the risk of irreversible vision loss. [34]

On the other hand, vitamin A is one of those nutrients that can easily cross the line between benefit and harm. Chronic excess retinol from supplements and frequent liver consumption can damage the liver and bones and increase the risk of certain diseases, especially in pregnant women. Therefore, self-administering high doses of vitamin A for long periods without medical supervision and supervision should not be considered safe. [35]

The optimal approach is to follow a varied diet: include moderate amounts of retinol-rich animal products and daily consumption of carotenoid-rich fruits and vegetables. This diet allows you to meet your daily vitamin A requirement without the risk of toxicity and also provides the body with other important micronutrients and dietary fiber. [36]

Vitamin A supplements are typically needed for specific medical purposes: treating a deficiency, participating in mass prevention programs in disadvantaged areas, or as part of combination therapy for diseases that impair absorption. In all these situations, the dosage and duration of supplementation should be determined by a specialist. This balanced approach allows for the utilization of vitamin A's benefits while minimizing the risks of excess. [37]