Basics of Vitamin A

Vitamin A: Functions, Forms, Food sources, Deficiency and Toxicity

What are the functions of vitamin A?

Stanfield and Hui (2011), define vitamins as a group of essential organic compounds required daily in very small amounts (mostly milligrams) for the normal functioning of the body. According to Ball (2008), Vitamins have unique varying functions in the body including the regulation of gene expression (Vitamins A and D, thiamin, vitamin B12), structural roles in visual pigments (vitamin A as retinal), function as anti-oxidants (vitamins A, E, and C) and, as enzyme cofactors (the B group vitamins and Vitamin K (Dryden, 2008). 

Vitamin A along with other fat soluble vitamins is found in foodstuffs in association with lipids and is absorbed along with dietary fats by mechanisms similar to fat absorption (McDowell, 2008).

According to Seth (2011), the various functional forms of vitamin A have  correspondingly different functions in the body. Retinol aids in transport and reproduction (Dente and Hopkins, 2010),  retinyl esters are important in storage, retinal plays a key role in vision whereas the function of retinoic acid is demonstrated in epithelial differentiation, growth and transformation. The most widely recognized role played by vitamin A is its function in vision (Combs, 2012). Retinol is utilized in the aldehyde form (trans-form to 11-cis-retinal) in the retina of the eye as the prosthetic group in rhodopsin for adaptation to darkness i.e. rods (Berdainer, 2010) and as the prosthetic group in iodopsin for bright light and color vision i.e. cones (McDowell, 2008). In maintenance of integrity of the cornea, retinoic acid is needed to sustain appropriate cell differentiation (Herrmann and Obeid, 2011).

Vitamin A has gained a reputation as an anti-infective vitamin (Whitney et al., 2011) essential for normal immune system maturation and function. There is evidence to suggest that vitamin A deficiency is a risk factor for low antibody production (Hulea, 2008) and,  that vitamin A plays a role in maintenance of integrity of  epithelial surfaces and development of  the lymphoid system (Shetty, 2010). Vitamin A stimulates antitumor activity in cancer cell lines. All-trans-retinoic acid exhibited an inhibitory effect on cell growth, cell cycle and alkaline phosphatase activity in human pancreatic cancer cells in vitro (Guo et al., 2006).

Vitamin A especially as retinoic acid is required for differentiation of epithelial cells. Cell differentiation is a process by which immature cells are transformed into specific type of mature cells, which form protective linings on many of the body’s organs (Gropper et al., 2009).  The integrity of the respiratory, gastrointestinal, and urogenital tracts, as well as the eye, are protected from environmental influences by mucous membranes (Elias and Ketcham 2007). Retinoids perform the latter function in a way that steroid hormones do; this is by binding to the nuclear chromatin to signal transcriptional processes. Further retinoic acid has been found to stimulate, synergistically with thyroid hormone, the production of growth hormone in cultured pituitary cells (Combs, 2012).

Vitamin A functions as an antioxidant to reduce markers of oxidative damage and inflammation, and therefore may be helpful in preventing initiation and progression of diseases due to oxidative stress (Prasad, 2008). Beta carotene is one of the many dietary anti-oxidants present in foods- others include, vitamin E, Vitamin C, the mineral selenium and various phytochemicals (Whitney et al., 2011). A study from 1989 to 1995 showed that higher serum levels of beta- carotene, total carotene, provitamin A and total carotenoid reduced the harzadous ratios for mortality rates of patients with cardiovascular diseases and cancer at all sites. (Ito et al., 2006).Vitamin A itself is physiologically significant in this regard, as retinol and retinal cannot quench singlet oxygen and have only weak capacities to scavenge free radicals. It however can affect tissue levels of other antioxidants. Several carotenoids, on the other hand, have been shown to have direct antioxidant activities. These include beta-carotene, lycopene and some oxycarotenoids (like lutein and zeaxanthin), which can quench singlet oxygen or free radicals in the lipid membranes into which they partition (Combs, 2012).

Forms and Sources of Vitamin A

Vitamin A is generally classified into two main groups possessing biological activity: (i) C-20 unsaturated hydrocarbons including retinol and its derivatives from animal origin (b) C-40 unsaturated hydrocarbons including carotene and a number of other provitamin A carotenoids of plant origin (Heldman and Lund, 2006).

Preformed vitamin A is found in foods of animal origin the richest sources being liver and fish oil. Milk and milk products and vitamin A fortified foods such as enriched cereals can also be good sources. Even butter and eggs provide some vitamin A (Sizer and Whitney, 2013).  Eating liver once a week or so is enough to provides the recommended daily intake. Butter and eggs also provide some vitamin A to the diet. Because vitamin A is fat soluble, it is lost when milk is skimmed. To compensate, reduced-fat, low-fat and fat-free milk are often fortified with vitamin A. Margerine is also usually fortified so as to provide the same amount of vitamin A as butter (Whitney et al., 2011).

Retinoids refer to any natural or synthetic form of vitamin A ( Messonnier, 2010). Retinol is the alcohol form of vitamin A. Replacement of the alcohol group by an aldehyde group gives retinal, and replacement by an acid group gives retinoic acid. Esters of retinol are called retinyl esters. Vitamin A in animal products exists in several forms, but the principally exists as long chain fatty acid esters (McDowell, 2008). In several varieties of seawater and freshwater fish, vitamin A2 is present as a major form of vitamin A. Vitamin A2 differs from vitamin A in chemical structure as it has an addition double bond in the cyclohexene ring at the 3,4 position ( Herrmann and obeid, 2011). The most active form of vitamin A is the all-trans vitamin A. the cis-forms may arise from the all trans-form, and there is a loss of vitamin A potency due to the conversion. These changes are promoted by moisture, heat, light and catalysts (McDowell, 2008).

Carotenoids are usually found in plants and plant products as in inactive forms. They are referred to as provitamin A or vitamin precursors because the body can convert them into active vitamin A (Insel et al., 2012). The carotenoids are a diverse group of more than 600 naturally occurring pigments. All of the carotenoids are antioxidants, and approximately 50 are considered vitamins because they have pro-vitamin A activity (Morley and Thomas, 2007). Four of these including α-carotene, β-carotene, γ-carotene, and cryptoxanthine have vitamin A activity of which β-carotene has the greatest activity. Theoretically, I mol of β-carotene could be converted to 2 mol of retinal whereas 1 mole of other provitamin A carotenoids yield only one mol of retinal (McDowell, 2008). Carotenoids can further be classified into provitamin A and non-provitamin A carotenoids. Provitamin A carotenoids include beta –carotene, alpha-carotene, gamma-carotene, beta-cryptoxanthin and alpha-cryptoxanthin (Victor, 2012). Provitamin A carotenoid absorption is usually low, at around 10-20% and not all absorbed provitamin A carotenoids are cleaved into vitamin A activitive compounds (Bohn, 2008). Non-provitamin A carotenoids include lutein, lycopene, zeaxanthin and astaxanthin and according to Sayo et al., (2013) the molecular basis of their biological activities is not fully known.

Many plant foods contain beta-carotene, the orange pigment responsible for the bold colors of many fruits and vegetables. Carrots, sweet potatoes, pumpkins, cantaloupe, and apricots are all rich sources and their bright orange color enhances the eye appeal of the plate. Dark green vegetables, such as spinach, other greens, and broccoli, owe their color to both chlorophyll and beta-carotene. However colorful vegetables like iceberg, lettuce, beets and sweet corn don’t contain beet carotene as it my perceived (Whitney et al., 2011). The vitamin A activity of fruits is generally lower than that of leafy vegetable. However fruits have more acceptance than vegetables especially in children.  Mango, papaya and watermelon have the highest concentration of provitamin A carotenoids (Sommerburg et al., 2013). The carotenoid content of foods is highly variable and is affected by a number of factors including genotype (variety and cultivar), season, geography, cultivation variation, stage of maturity at harvest, handling and postharvest storage conditions (Tanumihardjo, 2012).

Vitamin A and Night Vision

Vitamin A allows for night and color vision as is a functioning part of the retina. The retina contains both rod and cone cells. The former are of interest in low light vision and are rich in a purple pigment rhodopsin also known as visual purple (Insel et al., 2012). Retinol is utilized in the aldehyde form in the retina of the eye as the prosthetic group in rhodopsin for dim light vision (rods) (McDowell, 2008). Each rhodopsin molecule is composed of a protein called opsin bonded to a molecule of the retinal form of vitamin A (Whitney et al., 2011).

When light strikes rhodopsin, cis-retinal changes in configuration to trans-retinal, subsequently separating from opsin. This metabolic conversion, in turn, causes a series of reactions leading to a decrease in sodium entry to sodium channels and a change in membrane potential that is transmitted to the brain. This neural signal is seen as light and is transformed into an image that you recognize (Desai, 2000). A visual cycle is completed when trans-retinal is converted back to cis- retinal which in turn combines with opsin in the outer segment to form rhodopsin. (Gibney  et al., 2012). However, trans-retinal is not recycled to cis-retinal with 100% efficiency. Instead, some trans-retinal is converted to retinoic acid, which cannot be used to form rhodopsin. Extra retinal must therefore always be available for vision to remain optimal. Without enough retinal to reform, night vision becomes especially difficult, resulting in a condition called night blindness (Mcguire and Beerman, 2011).The role played by vitamin A in night vision (dark adaptation) is illustrated in figure 1.

Vitamin A Deficiency

McDowell (2008), states that vitamin A is one of the few vitamins whose deficiency or excessive amounts constitute a health hazard. Vitamin A deficiency affects over 250 million preschool children of which close to 500,000 become blind every year and half of them die within 12 months of losing their sight (WHO, 2013). The deficiency is more prevalent in the developing world due to inadequate intake whereas toxicity is commonly found in the developed world as a result of supplementation. Up to a year’s supply of vitamin A can be stored in the body, 90 percent of it in the liver (Whitney et al., 2013).  The extent of vitamin A deficiency can be assessed by biochemical measures such as plasma or serum retinol or retinol-binding concetrations (Semba and Bloem, 2008).

According to McDowell (2008), a diet deficient in Vitamin A causes lesions in the eye, the process of keratinization leads to drying and hardening of the cornea, which may progress to permanent blindness. Vitamin A deficiency is the major cause of preventable blindness in children (Whitney eta al, 2013),  loss of vision due to a failure of rhodopsin formation in the retina; defects in bone growth; defects in reproduction (e.g., failure of spermatogenesis in the male and resorption of the fetus in the female); and defects in growth and differentiation of epithelial tissues frequently resulting in keratinization of tissues including; the alimentary ,the genital, reproductive, respiratory and urinary tracts (McDowell, 2008).To prevent the severe deficiencies of vitamin A, the RDI is recommending 5,000 international units for men and women, and 8,000 international units for pregnant and lactating women (Bruning and Lieberman, 2007).

Vitamin A Toxicity

For optimum general health, the basic optimum daily intakes for Vitamin A are 5,000-25,000 IU for men and women respectively and for beta-carotene are 11,000-25,000IU for men and women respectively (Lieberman et al., 2007). Unlike the water soluble vitamins B and C that are easily eliminated from the body, vitamin A is fat soluble and therefore hard for the body to eliminate it (Asprey and Asprey, 2012). The hepatic storage of vitamin A tends to mitigate against the development of intoxication due to intakes in excess of physiological needs (combs, 2012). Both forms of active vitamin A i.e. both fat and water soluble are stored in the liver and can hence be toxic in excess amounts. However, toxicity is commonly due to persistent large overdoses of preformed vitamin A in foods derived from animals, fortified foods, or supplements (Whitney et al., 2011).  More than 1,000 times the nutritionally required amount can exceed the capacity of the liver to store and catabolize and will thus produce intoxication (Combs, 2012).

The condition attached to vitamin A toxicity is called hypervitaminosis A (Nix, 2012). It may be either acute or chronic. Acute toxicity usually follows a large single dose of vitamin A and is recognizes by symptoms suggesting an acute rise in intracranial pressure (McLaren and Kraemer, 2012). Acute symptoms may include; nausea, headache, fatigue, dizziness and loss of appetite. Chronic symptoms may include; dry skin, desquamation, cerebral edema, bone and joint pain, liver damage including cirrhosis, hemorrhages into the skin, and coma (Higdon and Drake, 2012). Natural beta-carotene, on the other hand, can be given for long periods of time virtually without risk of toxicity because the conversion of beta-carotene to active vitamin A is slow (Whitney et al., 2011). The only adverse effect of taking too much beta-carotene is the possibility of carotenemia, a harmless condition in which the skin turns a slight orange color (Lieberman et al., 2007). People take large doses of vitamin A with the aim of having improved vision, improved skin and resistance to disease. A pregnant woman who takes excess vitamin A is at a risk of miscarriages, or giving birth to a baby with malformations (Frankenburg, 2009). Too much vitamin A for a pregnant woman may disrupt a child’s brain cell activity. Vitamin A competes with vitamin D inside the body and therefore deprives the body of vitamin D creating a risk of osteoporosis (Asprey and Asprey, 2012).

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