What Does Vitamin A Do?

Vitamin A Foods

Humans cannot synthesize vitamin A on their own and can only get it from a diet of liver, fish, milk, eggs, and orange vegetables. Dietary molecules with VA activity are present in both preformed VA and provitamin A forms. Preformed VA is retinol and retinol-esters and is commonly obtained from foods of animal origin, with milk and dairy products and meat and meat products being the largest sources, followed by eggs, egg products and fish. Provitamin A carotenoids, on the other hand, come from foods of plant origin, and β-carotene is most abundant in the diet, which is mainly consumed through red and orange vegetables. Other sources of provitamin A carotenoids include various medicinal plants and herbs, grains, and specific vegetable oils.

Table 1. Content of β-carotene in selected sources

(Source: Carazo A, et al. 2021)

Retinyl-esters, the main storage form of VA, are digested in the gastrointestinal tract into retinol and fatty acids and absorbed by intestinal cells. Carotenoids in intestinal cells and hepatocytes are enzymatically converted to retinaldehyde mainly in the form of β-carotene, which is further processed and reduced to retinol. Esterification of retinol with fatty acids produces retinyl-esters, which enter the celiac microparticles, are transported in lymph and peripheral cells, and are transported through the bloodstream to the liver, where they circulate between hepatocytes and hepatic stellate cells (HSCs). Hepatic retinyl-esters are the best indicator of VA status.

The Food and Nutrition Board of the Institute of Medicine of the U.S. National Academy of Sciences has developed Dietary Reference Intakes (DRIs) for vitamin A. The Recommended Dietary Allowance (RDA) for vitamin A is expressed in μg, depending on age and sex. From 2021, it is recommended that VA intake be assessed using retinol activity equivalents (RAE), where 1µg RAE is equivalent to 1µg of retinol, 2µg of supplemental beta-carotene, 12µg of dietary β-carotene, or 24µg of dietary α-carotene or β-cryptoxanthin. For men, women, and pregnant women aged 19-50 years, the RDA for VA was 900, 700, and 770µg RAE, respectively.

Vitamin A Dosage

Excessive VA intake or VA deficiency can have serious consequences.

Table 2. Health risks and signs resulting from Vitamin A deficiency and excess intake of Vitamin A

(Source: Chen G, et al. 2023)

Vitamin A deficiency

Vitamin A deficiency is best characterized by impaired vision, which is especially noticeable in low light conditions. In extreme cases, the conjunctival and corneal epithelium loses its ability to differentiate due to a prolonged lack of VA, resulting in hyperkeratosis of the ocular epithelial tissue, which can eventually lead to permanent total blindness.

Vitamin A deficiency causes changes in the epithelium that directly affect several systems of the body and lead to weight loss. In the respiratory system, changes occur in the epithelium of the bronchial airways and the tissues become more susceptible to infection. Keratinization occurs in the skin, with epidermal dryness, followed by papules and keratinization of sweat glands. In the gastrointestinal tract, the number of goblet cells in the intestine decreases, epithelial cells are altered, and pancreatic ductal epithelial cells are metaplastic. The nervous system is also involved, and a portion of taste and olfactory function is mediated by the VA by mediating the synthesis of mucopolysaccharides, which are responsible for taste perception, and keratinization of this tissue leads to loss of taste and olfactory functions.

In addition, vitamin A deficiency is characterized by a general susceptibility to infection and inflammation. Symptoms are exacerbated by malnutrition, and blood transporter protein levels are decreased in malnourished children, further impairing vitamin A pharmacokinetics and corresponding function. VA also interferes with iron metabolism, and deficiency directly affects iron levels, leading to anemia.

Vitamin A toxicity

Excessive intake of vitamin A can lead to vitamin A toxicity, which is rare and may occur as a result of taking retinoids for therapeutic purposes. Hypervitaminosis was considered when the blood concentration of retinol in plasma was higher than 2.09 µM. Poisoning is usually associated with the misuse of dietary supplements, but can also occur after consuming more vitamin A-rich foods. Chronic toxicity occurs when adults consume 10 mg/day of vitamin A over a long period of time for several months, and when children consume 7.5-15 mg/day of vitamin A over a long period of time for several months. In addition, mild adverse effects (headache, irritability, fever, nausea, and vomiting) have been observed with vitamin A supplementation, but these are rare and usually resolve quickly after vitamin A intake is discontinued.

Acute vitamin A toxicity occurs when adults exceed 500mg/day or children exceed 100mg/day. Acute vitamin A toxicity is characterized by nausea, irritability, loss of appetite, vomiting, blurred vision, and headache. A less common manifestation of acute toxicity is intracranial hypertension, and idiopathic intracranial hypertension has been reported in patients who overdosed on VA or were treated with isotretinoin; this syndrome is characterized by headache, blurred vision, confusion, and elevated intracranial pressure.

The most common biochemical adverse reaction following administration of retinoid medications is hypertriglyceridemia, which typically occurs after several weeks of treatment, and subsequently these elevated triglyceride levels lead to liver damage, which can cause hepatic fibrosis and hepatic stellate cell activation, which may lead to irreversible liver damage. Oral vitamin A analogs can cause dry lips, headaches, flushing, stomach pain and loss of coordination.

In addition to the acute symptoms described above, patients with chronic poisoning may also experience insomnia, hypothyroidism, bone destruction, dry and itchy skin, and hepatosplenomegaly. An overdose of retinoids can lead to what is known as retinoid syndrome. This condition manifests itself as acute respiratory distress with dyspnea, pleural and pericardial effusions, fever, weight gain, edema, and even multi-organ failure.