Vitamin A – Structure, Functions, Properties, Source and deficiency

The retinoids, a group of molecules related to the dietary retinol  (vitamin A) , are essential for vision and reproduction, growth and the maintenance of epithelial tissue. They also play an essential part in the immune system. Retinoic acid, which is derived by oxidation of retinol plays a major role in the action of the retinoids. This is except for the function of vision which relies on the retinal, an aldehyde derivative of the retinol.

Vitamin A

• Vitamin A is the common name of a group of fat-soluble vitamins.
• The most widely used version of vitamin A is called retinol. It is also known as preformed vitamin A since it’s the most active version in the body.
• Retinol (an alcohol) is only found in the animal kingdom and is converted through the body’s metabolism into the retinal (an aldehyde) and the retinoic acid (a carboxylic acid) and other active forms of vitamin A.
• Vitamin A plays a variety of vital roles such as maintaining proper vision, enhancing bone growth , and other cellular processes such as cell division, reproduction and differentiation of cells.
• Vitamin A, which is fat-soluble, is only found in products of animals and carotenoids, a provitamin, can be found in plants.
• Vitamin A is a key part in the development and growth of human cells. It also regulates the immune system through stopping infection and activating white blood cells (WBCs) which destroy harmful pathogens.
• It is also linked with the development as well as the protection and growth of healthful surface liner areas that protect the respiratory tract, the intestinal tracts and urinary tracts . bacteria and other foreign species through the triggering of infections.
• Vitamin-A helps the mucous membranes and skin to act as a barrier against viruses and bacteria.
• The compound is commonly known as the antixerophthalmic factor , or the vitamin for bright eyes because of its importance in the process of visual perception.
• It has been noted and documented the fact that “Hippocrates of Kos”, an ancient Greek (about 500 BC) treated night blindness by giving his patients a vitamin-A diet. Vitamin- A was first discovered by a nutritionist known as “Christine Stumbock” in 1919.
• In 1917 “McCollum” and “Davis” discovered the fat-soluble component in vitaminA.
• Then in 1931, composition of the vitamin A was analyzed through “Karrer”, and its synthesizing process was carried out in the lab by “Kuhn” and “Morris” in 1937.
• Vitamin A is effective in treatments for Vitamin A deficiencies.

Requirements

Vitamin A requirements are dependent on the amount of intake required to maintain a normal blood level. Adults who are on a vitamin-A-free diet have no change in their level over a number of weeks.The ability that the body has to keep vitamin A makes the ability to provide an emergency supply. The recommended dosage of Vitamin A for various age groups is according to:

0 to 6 months old	400 micrograms (mcg)
7 to 12 months	500 mcg
1 to 3 years	300 mcg
4 to 8 years	400 mcg
9 to 13 years	600 mcg
14 to 18 years	900 mcg for males, 700 mcg for females
14 to 18 years/pregnant females	750 mcg
14 to 18 years/breastfeeding females	1,200 mcg
19+ years	900 for males, 700 for females
19+ years/pregnant females	770 mcg
19+ years/breast-feeding females	1,300 mcg

Structure of vitamin A

Vitamin A is frequently used as a generic term to describe a variety of chemically active substances. Retinoids are both synthetic and natural varieties of vitamin A which may or might not exhibit vitamin A-related activity.

Vitamin A (also known as retinol) is an outline of its structure on the right. Retinol is the first precursor to two vital active metabolites: retinal which plays an important role in the development of vision and retinoic acid that acts as an intracellular signal that alters the transcription of a range of genes. Vitamin A is not found in plants, but a lot of plants have carotenoids like beta-carotene which is transformed into vitamin A in the intestine, and other tissues.

• Retinol:  A principal alcohol that contains a b-ionone ring with an unsaturated side chain. It is present in the tissues of animals as a retinyl ester containing long-chain FAs.
• Retinal: It is an aldehyde that results from the oxidation process of Retinol. Retinal and retinol are able to be converted.
• Retinoic acid: Retinoic acid is the acid created by the oxidation process of the retinal. Retinoic acid is not reduced within the body. Consequently, it is not able to cause the formation of either retinal or retinol.
• β-Carotene: The plant foods in our diet contain b-carotene. It can be oxidatively broken down within the intestine, resulting in two retinal molecules. In humans, this conversion is not efficient, as the vitamin A activity of b-carotene is one-third the retinol activity.

Properties of Vitamin A

• It is a colorless and oily substance that is colorless and oily.
• Retinol is a hormone steroid that aids in the growth of cells and their differentiation.
• By careful fractionation, it has been isolated as needles of pale yellowish color.
• It is fat-soluble, but is insoluble when dissolved in water.
• The loss of vitamin A happens when cooking, canning, and freezing are less However, the oxidizing agent degrades it.
• It is destroyed when exposed to UV light.
• Retinol can be stored as retinyl esters in the tissues of animals.
• It develops an ethereal blue color in high levels of “antimony trichloride” (AnCl3). ( It is a key element in”The “Cataract” method used to identify vitamin A.

• Vitamin A absorbs UV light. It is most effective at 325 nm.
• It’s quite stable, even without light and air. In addition, it makes esters with more fatty acids.
• In addition, it’s a soluble within fat and solvents. However, it is insoluble in water.

Sources of vitamin A

Vitamin A can be found naturally in a wide variety of foods, and can be taken from both animal and plant sources. The vitamins are stored in fat tissues, and are referred to as fat-soluble vitamins.

• The preformed Vitamin- A is the source of the vitamins derived from animals. These vitamins are absorbed in the form of retinol. Retinol is the most useful and active form of vitamin A. The sources of preformed Vitamin A are liver and poultry, fish whole milk and other animal products.
• The provitamin-A carotenoid is a source of vitamins that are derived from plants. It contains vibrant vegetables and fruits such as green leafy vegetables, watermelon, sweet potato tomatoes, nuts, broccoli, and yellow-colored vegetables like pumpkin, carrot bell peppers squash, etc. The yellow and orange-coloured fruits that are ripe include mangos, papaya, guava and orange, apricots, and so on.

Absorption and transport of vitamin A

• Transport to the liver: Retinyl esters in our diets are hydrolyzed within the mucosa of the intestinal tract, releasing Retinol and FFAs. Retinol that is derived from esters as well as through the reduction and cleavage of carotenoids is converted to long-chain FAs within the intestinal mucosa. It is then secreted as part of chylomicrons to the lymphatic system. The chylomicrons that contain retinyl esters remnants are absorbed by and stored in the liver.

• Release from the liver: If needed, retinol gets removed from the liver and transferred to extrahepatic tissues via the plasma retinol binding protein (RBP). The retinol RBP complex binds the transport protein located on the surface of tissue cells in peripheral tissues which allows retinol to get into. Most tissues contain a cell Retinol-binding protein, which carries Retinol to the nucleus, where the vitamin performs its function in a manner similar to that of steroids.

Mechanism of action of vitamin A

• Vision: Vitamin A (all-trans Retinol) is converted by the retina to the 11-cis isomer of retinaldehyde (11-cis-retinal). 11-cis-retinal is a component of the retina by converting of light into neural signals that are necessary to see. 11-cis retina, when linked to opsin within rhodopsin is isomerized to all-trans-retinal via light. This is the process that causes the neural signal to the brain that allows the brain to perceive light. Trans-retinal then gets released from opsin , and then decreased to all-trans-retinol. All-trans-retinol can be isomerized into 11-cis when it is dark and later transformed into 11-cis-retinol. 11-cis retina recombines with opsin in order to form the rhodopsin. Vision loss or night blindness in low light is caused by an inability to synthesize the 11-cis retinal quickly.
• Epithelial differentiation: The function in the role of Vitamin A during epithelial differentiation, as in different physiological procedures, is it binding Vitamin A in two nuclear retinal receptors (retinoic acid receptors also known as RARs and retinoid X receptors, RXRs). These receptors act as factors activated by ligands that regulate the transcription of genes. If there isn’t sufficient Vitamin A to connect to these receptors, the natural cell growth and differentiation are disrupted.

Toxicity of vitamin A

• Because the vitamin A compound is fat-soluble, eliminating any excesses that are taken by way of diet is more difficult than for the water-soluble vitamins B and C. Therefore, vitamin A toxicity could cause. It can cause irritation, nausea, jaundice and eating disorders, anorexia (not as a misnomer with anorexia-nervosa or eating disorder) vomiting, blurred vision, headaches, and abdominal pains, fatigue, drowsiness and diminished mental health.
• The most common acute toxicity is doses of 25,000 IU/kg of body weight while chronic toxicity can be found at 4,000 IU/kg body weight per day for 6 to 15 weeks (Rosenbloom 2007).
• However, liver-related toxicities can be as low as 15,000 IU daily to 1.4 million IU per day. This is the average daily dosage at 120,000 IU per day. For people suffering from renal failure, 4000 IU could cause severe damage.
• Furthermore, alcohol consumption that is excessive can cause toxicity to increase. Children may reach toxic levels as high as 1500IU/kg body weight.
• In more severe cases, hair loss, dryness of mucous membranes fatigue, insomnia, fever bone fractures, weight loss as well as diarrhea and anemia may all be present in addition to the signs related to less serious toxicities.
• A long-term high dosage of Vitamin A can produce the condition known as “pseudotumor cerebri.” This condition can cause headaches, blurring of vision, headache and confusion. It is a result of increased intracerebral pressure.
• It is estimated at 75 per cent the population are taking higher than RDA of vitamin A daily basis in the developed countries. Consuming double the RDA of vitamin A performed regularly could be linked to hip fractures and osteoporosis.
• The intake of high vitamin A is associated with the occurrence of spontaneous fractures of bones in animals. Studies in cell culture have revealed the resorption of bone and the decrease of bone formation in the intake of high amounts of vitamin A. This could be due to vitamin A and D could be competing with each other for the same receptor. They later interact with parathyroid hormone that regulates calcium.
• Vitamin A’s toxic effects have been demonstrated to profoundly impact the development of fetuses. Treatment doses prescribed to treat acne have been proven to interfere with neural activity in the cephalic cortex. Fetuses are particularly vulnerable to the toxic effects of vitamin A during the time of organogenesis.
• The toxicities are only present in the preformed (retinoid) vitamin A (such as liver). The forms of carotenoid (such as beta-carotene, which is discovered in carrots) do not cause symptoms, however an excessive consumption of beta-carotene may cause carotenodermia. This causes an orange-yellow discoloration on the skin.

Researchers have made it possible to develop the water-soluble vitamin A which they believe can reduce the risk of toxic effects. However, a study from 2003 found that the water-soluble vitamin was about 10 times as harmful as fat-soluble vitamin. A study in 2006 revealed that children who received water-soluble vitamins D and A, both of which are usually fat-soluble, have twice as many than a group that was supplemented with fat-soluble vitamins.

Functions of Vitamin A

Vitamin A along with its various metabolites, retinal and acid have been shown to perform many crucial functions in physiology, as demonstrated by the variety of ailments which are caused by deficiency and excess conditions. In many instances, the the precise mechanisms of action aren’t fully identified. Some of the well-studied results of vitamin A are:

1. Vision

• Retinal is an essential structure component in rhodopsin, also known as visual purple, a light-sensitive pigment that is found in cone and rod cells of the retina. If a deficiency in vitamin A is present, sight may be affected.
• Bright, dark and color vision depend on the vitamin A’s activity.
• Rods are accountable in dim-light vision while cones play a role in bright light and color vision.

Dark adaptation time

• In the absence or absence of vit-A the dark adaptation period is longer.
• In the event that someone is ushered into a dimly lit room, the rhodopsin levels are reduced.
• The room is dark until and unless rhodopsin cannot be regenerated.
• To this end, it is necessary to have vit-A.

Color vision

• Cones are the primary source of color vision , such as Iodopsin (green) and the cyanopsin (blue) as well as porphyropsin (red).
• They also make up retinal complexes, and after bleaching, release various colors: blue, red and green that are sent as nerve impulses to the central nervous system.

2. Resistance to infectious disease

• In virtually every disease of infection studied in the study, vitamin A deficiencies have been found to increase the severity and frequency of illness.
• Numerous large studies with malnourished children have shown significant reductions in mortality due to illnesses like measles, for example. This is due to the easy and cost-effective method of supplementing vitamin A.
• Its “anti-infective” effect is undoubtedly complicated, but it is in part due to the need for vitamin A to support normal immune response.
• In addition, many illnesses result from an inflammatory response that results in lower levels of retinol binding protein, which results in lower levels of retinol in the bloodstream.

3. Epithelial cells “integrity”

• The epithelial cells of many types require vitamin A to ensure the proper development and for maintenance.
• The absence of vitamin A can lead to the dysfunction of numerous epithelia. Skin becomes more scaly and keratinized, and mucus secretion is reduced.
• It is likely that a lot of these symptoms are caused by impaired transcriptional regulation resulting from deficiencies in the retinoic acid signaling.
• Retinol and retinoic acids regulate/control the keratin gene, and thus stop the development of Keratinized (horny) surfaces.
• Similar to retinyl-phosphate, it is involved in the production of mucus (mucopolysaccharide) and glycoprotein which are essential to keep epithelial surfaces dry and smooth.

4. Bone remodeling

• The normal function of osteoblasts as well as osteoclasts depends on vitamin A.

5. Reproduction

• Vitamin A levels are normal and essential to produce sperm, indicating the need for vitamin A in the spermatogenic epithelial (Sertoli) cells.
• In the same way, normal reproduction in females requires the availability of vitamin A.

6. Cell differentiation and growth

• Retinol, retinoic acid and Retinol function as steroid hormones which regulate the development and differentiation of cells.

7. Lipid metabolism

• Mevalonate is an intermediate produced during the biosynthesis of cholesterol.
• In the absence or absence of vit-A mevalonate will be directed toward the production of coenzyme Q.

8. Other Functions

• In the absence of vitamin A in the absence of vit-A, glucocorticoids production is inhibited and this in turn hinders the process of gluconeogenesis.
• Vit-A is also necessary to ensure the proper functioning of the immune system as well as for the creation of iron transfer protein transferrin.

Vitamin A And Immune System

• Vitamin A (carotenoids) is a vitamin that has an anti-inflammatory effect and plays an important role in improving immunity. It has been proven to have therapeutic effects in treating a variety of infectious diseases.
• It was discovered that nutrients that are rich in vitamin A lower the risk of developing cancer however, its absence has been linked with the risk increase of contracting infections.
• Vitamin A is essential in the growth and function of B and T lymphocytes.
• Thus, a decline in the level of vitamin A naturally reduces immune cell reactions and also reduces specific antibodies after vaccination.
• It has been proven that vitamin A may also inhibit normal apoptosis of bone-marrow cells, resulting in an increased quantity of marrow cells found in the bone marrow as well as in spleen , and peripheral blood. This indicates that vitamin A plays a role in controlling the homeostasis of bone marrow.
• Vitamin A supplements also work as an adjuvant to boost immune responses when it is given during immunization. It was observed that vitamin A is essential for measles recovery in children.
• So, supplements with large doses of vitamin A that are administered within the first few days after hospitalization, greatly reduce the risk of dying and morbidity among children.
• The improved results were due to an increase in measles antibody tests in children receiving vitamin A supplements.
• Vitamin A supplements for children are identified to decrease the risk of dying and morbidity caused by certain types of measles, diarrhea, HIV disease and malaria.
• Additionally, recent studies have revealed a link between vitamin A deficiencies and infectious diseases like tuberculosis, AIDS and other infectious diseases that propagated through the digestive and respiratory systems of children.
• The exposure to UV radiation directly increases the burden of free radicals that is imposed on the body. It also reduces immune reactions, specifically cell-mediated reactions. It also raises the likelihood of developing skin cancer.
• However, b-Carotene as well as other carotenoids are able to block singlet oxygen production triggered from ultraviolet radiation. In fact, this singlet oxygen may trigger the creation of immunosuppression.

Clinical indications of Vitamin A

While chemically related, retinoic acids and Retinol have distinct uses for therapeutic purposes. Retinol as well as its carotenoid precursor are used as nutritional supplements, and the various forms of retinoic acids can be beneficial in dermatology.

1. Dietary deficiency

• Vitamin A is administered in the form of Retinol or retinyl ester, and can be used for treating patients deficient in vitamins.
• Night blindness is among the first symptoms of an A vitamin deficiency. The visual threshold increases and it becomes impossible to perceive in dark lighting.
• Deficiency for a long time can cause an irreparable decrease in the amount of visual cells. Vitamin A deficiency can lead to xerophthalmia which is a pathological dryness of the conjunctiva as well as cornea. It is caused in part by an increase in keratin synthesis.
• If not treated, xerophthalmia may result in corneal ulceration, and ultimately, blindness due to the formation of scar tissue that is opaque.
• The most common occurrence is observed in children living in tropical nations. More than 500,000 children around the world suffer from blindness each year as a result of the condition caused by a lack of vitamin A intake in their diet.

2. Acne and psoriasis

• Skin problems like acne and psoriasis are treated with retinoic acids and its derivatives.
• Mild cases of acne Darier disorder (keratosis follicularis) and skin aging can be treated by applications of tretinoin (all-trans Retinoic acid) and benzoyl-peroxide and antibiotics. (Note: Tretinoin is too toxic for administration through the system and is only used for topical applications).
• For patients suffering from severe acne that is not responsive to standard treatments the treatment that is recommended can be isotretinoin (13-cis Retinoic acid) given orally.
• Retinoic acid can also be utilized for the treatment of acute promyelocytic lymphoma.

Vitamin A Deficiency

Vitamin A deficiency is usually a result due to malnutrition. However, it could be caused by a defect in the digestion of carotenoids or retinol. Deficiency is common among human beings, particularly children, and in particular nations that are not developed. For herbivores, such as cattle, Vitamin A deficiencies are typically due to insufficient green feed, for instance, animals coming from dry summer pastures or those who are fed low quality hay. Since the liver stores huge amounts of retinol deficiencies typically take a few months to manifest. Some of the most serious symptoms that are a result of deficiency in vitamin A comprise:

• Blindness due to the inability to synthesize sufficient amounts of the rhodopsin. Deficiency can cause impairments in the ability to see under dim lighting (“night blindness”) and the severe deficiencies can cause extreme dryness and opaqueness of the cornea (xerophthalmia).
• The increased risk of death due to infectious diseases is most commonly studied in children with malnutrition, but also in animals. In these cases vitamin A supplementation has been found to dramatically reduce the risk of death from illnesses like measles or gastrointestinal diseases.
• The epithelial function is not as good as it should be for many cells, as evidenced by various conditions as dry, scaly , or dry skin insufficiency of mucosal surfaces, infertility diminished thyroid hormone production and elevated cerebrospinal pressure due to insufficient absorption of meninges.
• Bone growth that is abnormal in animals lacking vitamin A can result in malformations as well as, when skulls are affected, there can be problems that affect the central nervous system as well as optic nerve.

Vitamin A excess/Symptoms of hypervitaminosis A

The symptoms vary depending on whether the toxicity is acute or chronic. Itchy and red skin are typical in both forms of the disease.

The symptoms for acute vitamin A toxicities can include:

• Drool
• irritability
• Abdominal discomfort
• nausea
• vomiting
• Increased pressure on the brain

Signs that are a result of chronic vitamin A toxicity can be seen in:

• blurry vision, or other changes in vision
• The swelling of bones
• bone discomfort
• poor appetite
• dizziness
• nausea and vomiting
• The sensitivity of the sunlight
• rough, dry skin
• the skin is itchy or peeling
• cracked fingernails
• Skin cracks appear at the corners of your mouth.
• Mouth ulcers
• Skin that is yellowed (jaundice)
• hair loss
• respiratory infection
• confusion

For infants and children the symptoms could include:

• Softening of the skull bone
• The soft spot is bulging over the top of the skull of an infant (fontanel)
• double vision
• Eyeballs bulging in the eye
• Inability to lose weight
• Coma

In a soon-to-be pregnant woman, problems in their infant can be caused from a high level of vitamin A.

If you’re pregnant, do not consume more than one vitamin for prenatal use every day. There’s enough vitamin A present in the prenatal vitamin. If you require more iron, you can add one iron-rich supplement in your prenatal vitamins daily. Don’t take more than two prenatal vitamins as the chance of developing deformities for your baby is increased.

If you’re pregnant, do not apply retinol-based skin creams that are rich in Vitamin A.

The proper quantity of Vitamin A is essential in the growth of the fetus. But, excessive consumption of vitamin A during pregnancy can result in birth defects that could impact the eyes of a newborn baby and skull, lungs and even the heart.

References

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