Retinol, is one of the animal forms of vitamin A Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal. This molecule is absolutely necessary for both scotopic and color vision. In another version the vitamin is necessary for the function of the reproductive systems of both male and female mammals. Vitamin A also. It is a diterpenoid Terpenes are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium and an alcohol. It is convertable to other forms of vitamin A, but as retinol (the alcohol form) it is thought to serve an irreplaceable vitamin function in the reproductive tracts of male and female mammals. The retinyl ester Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. Basically, esters are derivative of the alcohol serves as the storage form of the vitamin in animals.

When converted to the retinal (aldehyde) form, vitamin A is essential in the vision The visual system is the part of the central nervous system which enables organisms to see, as well as enabling several non-image forming photoresponse functions. It interprets information from visible light to build a representation of the surrounding world. The visual system accomplishes a number of complex tasks, including the reception of, and when converted to retinoic acid Retinoic acid is the oxidized form of Vitamin A, with only partial vitamin A function. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. Retinoic acid acts by binding to heterodimers of the, is essential for skin health and bone Bones are rigid organs that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue. Because bones come in a variety of shapes and have a complex internal and external structure growth. These chemical compounds are collectively known as retinoids The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth, and possess the structural motif of all-trans retinol as a common feature in their structure. Structurally, all retinoids also possess a β-ionone The ionones are a series of closely related chemical substances that are part of a group of compounds known as rose ketones, which also includes damascones and damascenones. Ionones are aroma compounds found in a variety of essential oils, including rose oil. beta-Ionone is a significant contributor to the aroma of roses, despite its relatively ring and a polyunsaturated side chain, with either an alcohol In chemistry, an alcohol is any organic compound in which a hydroxyl functional group (-O , aldehyde An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl centre bonded to hydrogen and an R group. The group without R is called the aldehyde group or formyl group. Aldehydes differ from ketones in that the carbonyl is placed at the end of a carbon skeleton rather than, a carboxylic acid Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. A carboxyl group is a functional group consisting of a carbonyl and a hydroxyl, which has the formula -C(=O)OH, usually written -COOH or -CO2H. Carboxylic acids are Brønsted-Lowry acids — they are proton donors. Salts and anions of carboxylic acids group or an ester group. The side chain is composed of four isoprenoid The terpenoids , sometimes called isoprenoids, are a large and diverse class of naturally-occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon units, with a series of conjugated double bonds which may exist in trans- or cis-configuration.^[1]

Retinol is produced in the body from the hydrolysis of retinyl esters, and from the reduction of retinal. Retinol in turn is ingested in a precursor form; animal sources (liver The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function and eggs An egg is a spheroid or ovoid shaped cell laid by females of many different species, including birds, reptiles, amphibians, and fish. Eggs have been eaten by mankind for millennia. Bird eggs consist of a protective eggshell, albumen (egg white), and vitellus (egg yolk), contained within various thin membranes) contain retinyl esters Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. Basically, esters are, whereas plants Plants are living organisms belonging to the kingdom Plantae. They include familiar organisms such as trees, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The scientific study of plants, known as botany, has identified about 350,000 extant species of plants, defined as seed plants, bryophytes, ferns and fern allies. As of 2004, (carrots The carrot (Daucus carota subsp. sativus, Etymology: Middle French carotte, from Late Latin carōta, from Greek καρότον karōton, originally from the Indo-European root ker- , due to its horn-like shape) is a root vegetable, usually orange in colour, though purple, red, white, or yellow varieties exist. It has a crisp texture when fresh, spinach Spinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant (rarely biennial), which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions. The leaves are alternate, simple, ovate to triangular-based, very variable in size from about 2-30) contain pro-vitamin A carotenoids Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some types of fungus some bacteria and at least one species of aphid. Carotenoids are generally not manufactured by species in the animal kingdom, although one species of (these may also be considered simply vitamin A). Hydrolysis Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations (H+) (conventionally referred to as protons) and hydroxide anions (OH−) in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization. Such polymer of retinyl esters results in retinol, while pro-vitamin A carotenoids can be cleaved to produce retinal Retinal, also called retinaldehyde or vitamin A aldehyde, is one of the many forms of vitamin A . Retinal is a polyene chromophore, and bound to proteins called opsins, is the chemical basis of animal vision. Bound to proteins called type 1 rhodopsins, retinal allows certain microorganisms to convert light into metabolic energy. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid, which then cannot function as the vitamin in the eye or in the reproductive system.

Commercial production of retinol typically requires retinal synthesis through reduction of a pentadiene derivative and subsequent acidification/hydrolysis of the resulting isomer to produce retinol. Pure retinol is extremely sensitive to oxidization and is prepared and transported at low temperatures and oxygen free atmospheres. When prepared as a dietary supplement, retinol is stabilized as the ester Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. Basically, esters are derivatives retinyl acetate or retinyl palmitate Retinyl palmitate, or vitamin A palmitate is the ester of retinol and palmitic acid, with formula C36H60O2.^[2]

Discovery

In 1913, Elmer McCollum McCollum was born on a farm near Fort Scott, Kansas, where he spent his first seventeen years. He worked at odd jobs to finish high school and college, graduating from the University of Kansas in 1903 and earning his doctorate at Yale University in 1906. As a faculty member in agricultural chemistry at the University of Wisconsin, he established, a biochemist The most common "industry" role is to develop biochemical products and processes. This can be done by conducting in vitro research, analysis, synthesis and experimenting. Identifying substances' chemical and physical properties in biological systems is of great importance, and can be carried out by doing various types of analysis' at the University of Wisconsin–Madison, and colleague Marguerite Davis identified a fat-soluble nutrient in butterfat Butterfat or milkfat is the fatty portion of milk. Milk and cream are often sold according to the amount of butterfat they contain and cod liver oil Cod liver oil is a nutritional supplement derived from liver of cod fish. It has high levels of the omega-3 fatty acids, EPA and DHA, and very high levels of vitamin A and vitamin D. It is widely taken to ease the symptoms of arthritis and for other health benefits. It was once commonly given to children, because the high levels of vitamin D in. Their work confirmed that of Thomas Osborne and Lafayette Mendel Lafayette Benedict Mendel was an American biochemist known for his work in nutrition including the study of Vitamin A, Vitamin B, lysine and tryptophan, at Yale Yale University is a private research university in New Haven, Connecticut, and a member of the Ivy League. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States. Yale has produced many notable alumni, including five U.S. presidents, nineteen U.S. Supreme Court, which suggested a fat-soluble nutrient in butterfat, also in 1913.^[3] Vitamin A was first synthesized in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.

Although the vitamin A was not identified until the 20th century, written observations of conditions created by deficiency of this nutrient appeared much earlier in history. Sommer (2008) classified historical accounts related to vitamin A and/or manifestations of deficiency as follows: "Ancient" accounts; 18th- to 19th-century clinical descriptions (and their purported etiologic associations); early 20th-century laboratory animal experiments, and clinical and epidiomologic observations that identified the existence of this unique nutrient and manifestations of its deficiency.^[4]

Chemical structure and function

Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a trans In organic chemistry, cis-trans isomerism or geometric isomerism or configuration isomerism or E-Z isomerism is a form of stereoisomerism describing the orientation of functional groups within a molecule. In general, such isomers contain double bonds, which cannot rotate, but they can also arise from ring structures, wherein the rotation of bonds or cis In organic chemistry, cis-trans isomerism or geometric isomerism or configuration isomerism or E-Z isomerism is a form of stereoisomerism describing the orientation of functional groups within a molecule. In general, such isomers contain double bonds, which cannot rotate, but they can also arise from ring structures, wherein the rotation of bonds configuration of four of the five double bonds A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, and other covalent bonds. In short, the attraction-to-repulsion stability that forms between atoms when they share electrons is known as covalent bonding found in the polyene Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds. These double carbon-carbon bonds interact in a process known as conjugation, which results in an overall lower energy state of the molecule chain. The cis isomers are less stable and can readily convert to the all-trans configuration (as seen in the structure of all-trans-retinol shown here). Nevertheless, some cis isomers are found naturally and carry out essential functions. For example, the 11-cis-retinal isomer is the chromophore A chromophore is the part of a molecule responsible for its color. The color arises when a molecule absorbs certain wavelengths of visible light and transmits or reflects others. The chromophore is a region in the molecule where the energy difference between two different molecular orbitals falls within the range of the visible spectrum. Visible of rhodopsin Rhodopsin, also known as visual purple, is a pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light, enabling vision in low-light conditions. Exposed to light, the, the vertebrate Vertebrates are members of the subphylum Vertebrata, chordates with backbones and spinal columns. About 58,000 species of vertebrates have been currently described. Vertebrata is the largest subphylum of chordates, and contains many familiar groups of large land animals. Vertebrates are comprised of animals from the groups jawless fishs, bony fish, photoreceptor molecule. Rhodopsin is composed of the 11-cis-retinal covalently linked via a Schiff base A Schiff base , named after Hugo Schiff, is a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group—but not hydrogen. Schiff bases are of the general formula R1R2C=N-R3, where R3 is an aryl or alkyl group that makes the Schiff base a stable imine. A Schiff base derived from an to the opsin Opsins are a group of light-sensitive 35-55 kDa membrane-bound G protein-coupled receptors of the retinylidene protein family found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction protein (either rod opsin or blue, red or green cone opsins). The process of vision relies on the light-induced isomerisation of the chromophore from 11-cis to all-trans resulting in a change of the conformation and activation of the photoreceptor molecule. One of the earliest signs of vitamin A deficiency is night-blindness followed by decreased visual acuity.

George Wald George Wald was an American scientist who is best known for his work with pigments in the retina. He won a share of the 1967 Nobel Prize in Physiology or Medicine with Haldan Keffer Hartline and Ragnar Granit won the 1967 Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Physics, Chemistry, Literature, Peace, and Physiology or Medicine since 1901. The first Nobel Prize in Physiology or for his work with retina The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses. These pigments (also called visual pigments), which led to the understanding of the role of vitamin A in vision.

Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating intracellular retinoic acid receptors The retinoic acid receptor is a type of nuclear receptor which is activated by both all-trans retinoic acid and 9-cis retinoic acid. There are three retinoic acid receptors (RAR), RAR-alpha, RAR-beta, and RAR-gamma encoded by the RARA, RARB, RARG genes respectively. Each receptor isoform has several splice variants: two- for alpha, four- for beta. The non-visual functions of vitamin A are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal vitamin A in their diet.

Role in embryology

Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos. During development there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond differently to retinoic acid depending on the amount present. For example, in vertebrates the hindbrain transiently forms eight rhombomers and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead rhombomeres 1-4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Hox genes which encode different homeodomain transcription factors which in turn can turn on cell type specific genes. Deletion of the Hox-1 gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2. The retina is also patterned by retinoic acid, with a concentration gradient that is high on the ventral side of the retina and low on the dorsal side.

Stem cell biology

Retinoic acid is an influential factor used in differentiation In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a single zygote to a complex system of tissues and cell types. Differentiation is a common of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways. It is thought to initiate differentiation into a number of different cell lineages by unsequestering certain sequences in the genome.

It has numerous applications in the experimental induction of stem cell differentiation; amongst these are the differentiation of human embryonic stem cells Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells to posterior foregut lineages and also to functional motor neurons In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system (or CNS) that project their axons outside the CNS and directly or indirectly control muscles. The motor neuron is often associated with efferent neuron, primary neuron, or alpha motor neurons.

Vision

Vitamin A is required in the production of rhodopsin Rhodopsin, also known as visual purple, is a pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light, enabling vision in low-light conditions. Exposed to light, the, the visual pigment used in low light levels. This is why eating foods rich in vitamin A is often said to allow an individual to see in the dark.

Epithelial cells

Vitamin A is essential for the correct functioning of epithelial cells In biology and medicine, an epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body. Many glands are also formed from epithelial tissue. It lies on top of connective tissue, and the two layers are separated by a basement membrane. In vitamin A deficiency, mucus-secreting cells are replaced by keratin Keratin refers to a family of fibrous structural proteins. Keratin is the key structural material making up the outer layer of human skin. It is also the key structural component of hair and nails. Keratin monomers assemble into bundles to form intermediate filaments, which are tough and insoluble and form strong unmineralized tissues found in producing cells, leading to xerosis.

Glycoprotein synthesis

Glycoprotein Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending extracellularly, the extracellular segments are often synthesis requires adequate vitamin A status. In severe vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.

Immune system

Vitamin A is essential to maintain intact epithelial tissues as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems. These include the lymphocytes (B-cells, T-cells, and natural killer cells), as well as many myelocytes (neutrophils, macrophages, and myeloid dendritic cells).

Formation of red blood cells (Haematopoiesis)

Vitamin A may be needed for normal haematopoiesis; deficiency causes abnormalities in iron metabolism.

Growth

Vitamin A affects the production of human growth hormone.

Clinical use

All retinoid forms of vitamin A are used in cosmetic and medical applications applied to the skin. Retinoic acid, termed Tretinoin in clinical usage, is used in the treatment of acne and keratosis pilaris in a topical cream. An isomer of tretinoin, isotretinoin is also used orally (under the trade names Accutane and Roaccutane), generally for severe or recalcitrant acne.

In cosmetics, vitamin A derivatives are used as anti-aging chemicals- vitamin A is absorbed through the skin and increases the rate of skin turnover, and gives an increase in collagen giving a more youthful appearance^[5]

Tretinoin, under the alternative name of all-trans retinoic acid (ATRA), is used as chemotherapy for acute promyelocytic leukemia, a subtype of acute myelogenous leukemia. This is because cells of this subtype of leukemia are sensitive to agonists of the retinoic acid receptors (RARs).

Units of measurement

When referring to dietary allowances or nutritional science, retinol is usually measured in international units (IU). IU refers to biological activity and therefore is unique to each individual compound, however 1 IU of retinol is equivalent to approximately 0.3 micrograms (300 nanograms).

Nutrition

This vitamin plays an essential role in vision, particularly night vision, normal bone and tooth development, reproduction, and the health of skin and mucous membranes (the mucus-secreting layer that lines body regions such as the respiratory tract). Vitamin A also acts in the body as an antioxidant, a protective chemical that may reduce the risk of certain cancers.

There are two sources of dietary vitamin A. Active forms, which are immediately available to the body are obtained from animal products. These are known as retinoids and include retinal and retinol. Precursors, also known as provitamins, which must be converted to active forms by the body, are obtained from fruits and vegetables containing yellow, orange and dark green pigments, known as carotenoids, the most well-known being beta-carotene. For this reason, amounts of vitamin A are measured in Retinal Equivalents (RE). One RE is equivalent to 0.001 mg of retinal, or 0.006 mg of beta-carotene, or 3.3 International Units of vitamin A.

In the intestine, vitamin A is protected from being chemically changed by vitamin E. Vitamin A is fat-soluble and can be stored in the body. Most of the vitamin A you eat is stored in the liver. When required by a particular part of the body, the liver releases some vitamin A, which is carried by the blood and delivered to the target cells and tissues.

Dietary intake

The Dietary Reference Intake (DRI) Recommended Daily Amount (RDA) for vitamin A for a 25-year old male is 900 micrograms/day, or 3000 IU.

Estimates have changed over time of the rate at which β-carotene is converted to vitamin A in the human body. An early estimate of 6:1 was revised to 12:1 and from recent studies and experimental trials carried out in developing nations it was revised again to 21:1^[6]. The implication of the reduced estimate is that larger quantities of β-carotene are needed to yield the necessary dietary requirement of vitamin A. This means that more continents are affected by the deficiency of vitamin A than was previously thought. Changing dietary choices in Africa, Asia, and South America will not be sufficient, and agricultural practices on those continents will need to change^[6].

The Food Standards Agency states that an average adult should not consume more than 1500 micrograms (5000 IU) per day, because this increases the chance of osteoporosis.

During the absorption process in the intestines, retinol is incorporated into chylomicrons as the ester form, and it is these particles that mediate transport to the liver. Liver cells (hepatocytes) store vitamin A as the ester, and when retinol is needed in other tissues, it is de-esterifed and released into the blood as the alcohol. Retinol then attaches to a serum carrier, retinol binding protein, for transport to target tissues. A binding protein inside cells, cellular retinoic acid binding protein, serves to store and move retinoic acid intracellularly. Carotenoid bioavailability ranges between 1/5 to 1/10 of retinol's. Carotenoids are better absorbed when ingested as part of a fatty meal. Also, the carotenoids in vegetables, especially those with tough cell walls (e.g. carrots), are better absorbed when these cell walls are broken up by cooking or mincing.

Deficiency

Vitamin A deficiency is common in developing countries but rarely seen in developed countries. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A. Night blindness is one of the first signs of vitamin A deficiency. Vitamin A deficiency contributes to blindness by making the cornea very dry and damaging the retina and cornea.

Interventions/remedies

Interventions or remedies in vitamin A deficiency in a deficient population may be enforced using three approaches:(A) through dietary modification involving the adjustment of menu choices of affected persons from available food sources to optimize vitamin A content, (B) enriching commonly eaten and affordable foods with vitamin A, a process called fortification. It involves addition of synthetic vitamin A to staple foods like margarine, bread, flours, cereals and other infant formulae during processing and (C) giving high-doses of vitamin A to the targeted deficient population, a method known as supplementation.^[7] Caution should however be exercised when using supplementation as a method of replenishing vitamin A in the body so that upper harmful limits are not attained.

Retinoid overdose (toxicity)

see Hypervitaminosis A for details

The Tolerable Upper Intake Level (UL) for vitamin A, for a 25-year old male, is 3,000 micrograms/day, or about 10,000 IU.

Too much vitamin A in retinoid form can be harmful or fatal, resulting in what is known as hypervitaminosis A. The body converts the dimerized form, carotene, into vitamin A as it is needed, therefore high levels of carotene are not toxic compared to the ester (animal) forms. The livers of certain animals, especially those adapted to polar environments, often contain amounts of vitamin A that would be toxic to humans. Thus, vitamin A toxicity is typically reported in Arctic explorers and people taking large doses of synthetic vitamin A. The first documented death due to vitamin A poisoning was Xavier Mertz, a Swiss scientist who died in January 1913 on an Antarctic expedition that had lost its food supplies and fell to eating its sled dogs. Mertz consumed lethal amounts of vitamin A by eating the dogs' livers.^[8]

Vitamin A toxicity occurs when an individual ingests vitamin A in large amounts more than the daily recommended value in the threshold of 25,000 IU/Kg or more. Often, the individual consumes about 3-4 times the RDA's specification ^[9] Toxicity of vitamin A is believed to be associated with the intervention methods used to upgrade vitamin A levels in the body such as food modification, fortification and supplementation, all of which are employed to combat vitamin A deficiency ^[10] Toxicity is classified into two categories: acute and chronic toxicities. The former occurs few hours or days after ingestion of large amounts of vitamin A accidentally or via inappropriate therapy. The later toxicity (Chronic) takes place when about 25,000 IU/Kg or more of vitamin A is consumed for a prolonged period of time. Symptoms associated with both toxicities include, but not limited to nausea, blurred vision, fatigue, weight-loss, menstrual abnormalities etc.^[11]

If eaten in one meal, 30 to 90 grams of polar bear liver is enough to kill a human being, or to make even sled dogs very ill.^[12]

Excess vitamin A has also been suspected to be a contributor to osteoporosis. This seems to happen at much lower doses than those required to induce acute intoxication. Only preformed vitamin A can cause these problems, because the conversion of carotenoids into vitamin A is downregulated when physiological requirements are met. An excessive uptake of carotenoids can, however, cause carotenosis.

The carotenoid beta-carotene was interestingly associated with an increase in lung cancer when it was studied in a lung cancer prevention trial in male smokers. In non-smokers, the opposite effect has been noted.

Excess preformed vitamin A during early pregnancy has also been associated with a significant increase in birth defects.^[13] These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects.^[14] The FDA currently recommends that pregnant women get their vitamin A from foods containing beta carotene and that they should ensure that they consume no more than 5,000 IU of preformed vitamin A (if any) per day. Although vitamin A is necessary for fetal development, most women carry stores of vitamin A in their fat cells, so oversupplementation should be strictly avoided.

A review of all randomized controlled trials in the scientific literature by the Cochrane Collaboration published in JAMA in 2007 found that supplementation with beta-carotene or vitamin increased mortality by 5% and 16%, respectively.^[15]

Contrary to earlier observations, recent studies emerging from some developing countries (India, Bangladesh and Indonesia) have strongly suggested that dosing expectant mothers in the population in which vitamin A deficiency is common and maternal mortality is high can greatly reduce maternal mortality ratio ^[16] Similarly, dosing newborn infants with 50,000 IU (15 mg) of vitamin A within 2 days of birth, can significantly reduce neonatal mortality ^[17]

Sources

All sources of vitamin A can provide retinol, but retinoids are found naturally in some foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75–7 oz (50–200 g):

• Cod liver oil
• Butter, Margarine
• Liver (beef, pork, chicken, turkey, fish)
• Eggs
• Cheese, Milk^[18]

Synthetic sources

Synthetic retinol is marketed under the following trade names: Acon, Afaxin, Agiolan, Alphalin, Anatola, Aoral, Apexol, Apostavit, Atav, Avibon, Avita, Avitol, Axerol, Dohyfral A, Epiteliol, Nio-A-Let, Prepalin, Testavol, Vaflol, Vi-Alpha, Vitpex, Vogan, and Vogan-Neu.

Night vision

Night blindness—the inability to see well in dim light—is associated with a deficiency of vitamin A. At first, the most light sensitive (containing more retinal) protein rhodopsin is influenced. Less pigmented by retinal iodopsins (three forms/colors in humans), responsible for color vision and sensing relatively high light intensities (day vision), are less impaired at early stages of the vitamin A deficiency. All these protein-pigment complexes are located in the light-sensing cells in eye's retina.

When stimulated by light, rhodopsin splits into a protein and a cofactor: opsin and all-trans-retinal (a form of vitamin A). The regeneration of active rhodopsin requires opsin and 11-cis-retinal. The regeneration of 11-cis-retinal occurs in vertebrates via a sequence of chemical transformations that constitute "the visual cycle" and which occurs primarily in the retinal pigmented epithelial cells.

Without adequate amounts of retinal, regeneration of rhodopsin is incomplete and night blindness occurs.

Closely related chemicals

• Tretinoin (Tradename: Retin-A)
• Isotretinoin (Tradename: Accutane(US), Roaccutane)
• Retinyl palmitate ("vitamin A palmitate")

Genetically engineered vitamin A enriched rice

Due to the high prevalence of vitamin A deficiency in developing countries, there are efforts to produce genetically modified rice rich in beta carotene. The idea is that this would help poor people, who can not afford a varied diet containing sufficient natural sources of vitamin A, meet their dietary needs. The golden rice project is one such effort, and is already undergoing trials.

References

1. ^ Gropper, S.S; Smith,J.L and Groff, J.L(2009). Advanced Nutrition and Human Metabolism 5th Edition Pp373-1182.
2. ^ Retinol Essential Actives, KAVI.
3. ^ Semba RD. Vitamin A as "Anti-Infective" Therapy, 1920–1940. Journal of Nutrition. 1999;129:783-791. PMID 10203551. Full Text Available
4. ^ Sommer, A(2008). Vitamin A Deficiency and Clinical Disease: An Historical Overview. J Nutr. 138:1835-1839.
5. ^ Archives of Dermatology
6. ^ ^{a b} Sommer, A(2008). Vitamin A Deficiency and Clinical Disease: An Historical Overview. J. Nutr. 138:1835-1839. http://www.ncbi.nlm.nih.gov/pubmed/18806089
7. ^ Schultink, W(2002). Use of Under-Five Mortality Rate As an Indicator for Vitamin A Deficiency in a Population. Proceedings of the XX International Vitamin A Consultative Group Meeting. J Nutr. 132:2881S-2883S.
8. ^ An account of Mertz's illness, retrieved 20 June 2007.
9. ^ Gropper,S.S., Smith, J.L and Groff, J.L(2009). Advanced Nutrition and Human Metabolism. 5th Edition. Pp 373-1182.
10. ^ Thompson, J and Manore, M (2005).Nutrients involved in antioxidant function.Nutrition: An Applied Approach. Pearson Education Inc. Publishers. Chp.8: 276-283.
11. ^ Mohsen, S.E., Mckinney, K and Shanti, M.S(2008). Vitamin A toxicity. http://emedicine.medscape.com/article/126104-follow-up.
12. ^ A. Aggrawal, Death by Vitamin A
13. ^ Challem, Jack, Caution Urged With Vitamin A in Pregnancy: But Beta-Carotene is Safe, The Nutrition Reporter Newsletter, 1995, retrieved 20 June 2007.
14. ^ Stone, Brad. Vitamin A and Birth Defects, 6 October 1995, retrieved 20 June 2007.
15. ^ Bjelakovic et al., Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis, JAMA, 297:842; February 28, 2007.
16. ^ Sommer, A(2008). Vitamin A Deficiency and Clinical Disease: An Historical Overview. J. Nutr.138:1835-1839.
17. ^ Tielsch, J.M, Rahmathullah, L., Thulsiraj, R.D., Katz, J., Coles, C., Sheeladevi, S., John, R and Prakash, K(2007). Newborn vitamin A dosing reduces the case fatality but not incidence of common childhood morbidities in South India. J Nutr. 132: 2470-2474; Klemm, R.D., Labrique, A.B., Christian, P., Rashid, M., Shamim, A.A., Katz, J., Sommer, A and West, K.P(2008). Newborn vitamin A supplementation reduced infant mortality in rural Bangladesh. 122: e242-e250.
18. ^ ** Brown, J. E(2002). Vitamins and Your Health. Nutrition Now. 3rd Edition. Pp 20-1 to 20-20.

External links

• Jane Higdon, "Vitamin A", Micronutrient Information Center, Linus Pauling Institute
• A commoningly used ingredient to lighten hyper-pigmentation
• NIH Office of Dietary Supplements - Vitamin A
• Retinol binding protein
• Merck Manual of Diagnosis and Therapy: Vitamin A Deficiency
• WHO publications on Vitamin A Deficiency
• BBC News article on Retinol's use as an anti-wrinkle cream

Categories: Vitamins | Alcohols | Retinoids | Antioxidants | Diterpenes

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