Vitamin A is linked to a family of similarly shaped molecules, the retinoids, which complete the remainder of the vitamin sequence. Its important part is the retinyl group, which can be found in several forms. In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl palmitate, which is converted to an alcohol (retinol) in the small intestine. Vitamin A can also exist as an aldehyde (retinal). The acid (retinoic acid), a metabolite, has only partial vitamin A activity, and does not function in the retina. Precursors to the vitamin (provitamins) are present in foods of plant origin as three of the members of the carotenoid family of compounds.

All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached. This structure is essential for vitamin activity.[1] The orange pigment of carrots - beta-carotene - can be represented as two connected retinyl groups, which are used in the body to contribute to vitamin A levels. Alpha-carotene and gamma-carotene also have a single retinyl group which give them some vitamin activity. None of the other carotenes have vitamin activity. The carotenoid beta-cryptoxanthin possesses an ionone group and has vitamin activity in humans.

The retinyl group, when attached to a specific protein, is the only primary light absorber in visual perception, and the compound name is related to the retina of the eye. The retinyl group also functions in retinoic acid, which exhibits hormone-like activities in other parts of the body.

Vitamin A can be found in various forms:

Retinol, the form of vitamin A absorbed when eating animal food sources, is a yellow, fat-soluble, vitamin with importance in vision and bone growth. Since the alcohol form is unstable, the vitamin is usually produced and administered in a form of retinyl acetate or palmitate.

Other retinoids, a class of chemical compounds that are related chemically to vitamin A, are used in medicine.

The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta-ionone rings), but no other carotenoids, function as vitamin A in herbivores and omnivore animals, which possess the enzyme required to convert these compounds to retinal. Carnivores in general are poor converters of ionine-containg carotenoids, and pure carnivores such as cats and ferets lack beta-carotene 15,15'-monooxygenase and cannot convert any carotenoids to retinals (resulting in no carotenoids being forms of vitamin A for these species).

Deficiency

Vitamin A deficiency is estimated to affect millions of children around the world. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern. With the high prevalence of vitamin A deficiency, the WHO has implemented several initiatives for supplementation of vitamin A in developing countries. Some of these strategies include intake of vitamin A through a combination of breast feeding, dietary intake, food fortification, and supplementation. Through the efforts of WHO and its partners, an estimated 1.25 million deaths since 1998 in 40 countries due to vitamin A deficiency have been averted.

Vitamin A deficiency can occur as either a primary or secondary deficiency. A primary vitamin A deficiency occurs among children and adults who do not consume an adequate intake of yellow and green vegetables, fruits and liver. Early weaning can also increase the risk of vitamin A deficiency. Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, low fat diets, and chronic exposure to oxidants, such as cigarette smoke. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor utilization of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and the oxidation of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the risk of vitamin A deficiency and lead to several physiological events. A study in Burkina Faso showed major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children.

Since the unique function of retinyl group is the light absorption in retinylidene protein, one of the earliest and specific manifestations of vitamin A deficiency is impaired vision, particularly in reduced light - night blindness. Persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes. Some other ocular changes are referred to as xerophthalmia. First there is dryness of the conjunctiva (xerosis) as the normal lacrimal and mucus secreting epithelium is replaced by a keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques (Bitot's spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and total blindness. Other changes include impaired immunity, hypokeratosis (white lumps at hair follicles), keratosis pilaris and squamous metaplasia of the epithelium lining the upper respiratory passages and urinary bladder to a keratinized epithelium. With relations to dentistry, a deficiency in Vitamin A leads to enamel hypoplasia.

Adequate supply of Vitamin A is especially important for pregnant and breastfeeding women, since deficiencies cannot be compensated by postnatal supplementation.

Toxicity


Since vitamin A is fat-soluble, disposing of any excesses taken in through diet is much harder than with water-soluble vitamins B and C, thus vitamin A toxicity may result. This can lead to nausea, jaundice, irritability, anorexia (not to be confused with anorexia nervosa, the eating disorder), vomiting, blurry vision, headaches, hairloss, muscle and abdominal pain and weakness, drowsiness and altered mental status.

Acute toxicity generally occurs at doses of 25,000 IU/kg of body weight, with chronic toxicity occurring at 4,000 IU/kg of body weight daily for 6–15 months. However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day. In people with renal failure 4000 IU can cause substantial damage. Additionally excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1500IU/kg of body weight.

In chronic cases, hair loss, dry skin, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity.

It has been estimated that 75% of people may be ingesting more than the RDA for vitamin A on a regular basis in developed nations. Intake of twice the RDA of preformed vitamin A chronically may be associated with osteoporosis and hip fractures. This may be due to the fact that an excess of vitamin A can block the expression of certain proteins that are dependent on vitamin K. This could hypothetically reduce the efficacy of vitamin D, which has a proven role in the prevention of osteoporosis and also depends on vitamin K for proper utilization.

High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high vitamin A intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyroid hormone which regulates calcium. Indeed, a study by Forsmo et al. shows a correlation between low bone mineral density and too high intake of vitamin A.

Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis.

These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, but excessive dietary intake of beta-carotene can lead to carotenodermia, which causes orange-yellow discoloration of the skin.

Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity. However, a 2003 study found that water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin. A 2006 study found that children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins.

Chronically high doses of Vitamin A can produce the syndrome of "pseudotumor cerebri". This syndrome includes headache, blurring of vision and confusion. It is associated with increased intracerebral pressure.