Retinol
Clinical data | |
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AHFS/Drugs.com | Monograph |
License data | |
intramuscular[1] | |
Drug class | vitamin |
ATC code | |
Legal status | |
Legal status |
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Identifiers | |
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JSmol) | |
Melting point | 62–64 °C (144–147 °F) |
Boiling point | 137–138 °C (279–280 °F) (10−6 mm Hg) |
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Retinol, also called vitamin A1, is a fat-soluble
Retinol at normal doses is well tolerated.[1] High doses may cause enlargement of the liver, dry skin, and hypervitaminosis A.[1][4] High doses during pregnancy may harm the fetus.[1] The body converts retinol to retinal and retinoic acid, through which it acts.[2]
Retinol was discovered in 1909, isolated in 1931, and first made in 1947.
Medical uses
Retinol is used to treat vitamin A deficiency.
Three approaches may be used when populations have low vitamin A levels:[10]
- Through dietary modification involving the adjustment of menu choices of affected persons from available food sources to optimize vitamin A content.
- 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 infant formula during processing.
- By giving high-doses of vitamin A to the targeted deficient population, a method known as supplementation. In regions where deficiency is common, a single large dose is recommended to those at high risk twice a year.[11]
Retinol is also used to reduce the risk of complications in measles patients.[11]
Side effects
The Recommended Daily Intake (RDA) for preformed supplemental Vitamin A for adult men and women is 900 and 700 Retinol Activity Units(RAE)/day, respectively, or about 3,000 IU and 2,300 IU. For pregnant people, the Vitamin A RDA is 750-770 RAE/day (about 2,500-2,550 IU). During lactation, the RDA increases to 1,200-1,300 RAE/day (about 4,000-4,300 IU).
Retinol Activity Units can only be converted to IU (International Units) when the source of the Vitamin A is known. The IU values listed above do not apply to food sources of Vitamin A.[12]
Too much vitamin A in retinoid form can be harmful. The body converts the dimerized form, carotene, into vitamin A as it is needed, so high levels of carotene are not toxic, whereas the ester (animal) forms are. The livers of certain animals, especially those adapted to polar environments, such as polar bears and seals,[13] 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 possibly caused by vitamin A poisoning was that of 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 may have consumed lethal amounts of vitamin A by eating the dogs' livers.[14]
Vitamin A acute toxicity occurs when a person ingests vitamin A in large amounts more than the daily recommended value in the threshold of 25,000 IU/kg or more. Often, the patient consumes about 3–4 times the RDA's specification.[15] Toxicity of vitamin A is believed to be associated with the methods of increasing vitamin A in the body, such as food modification, fortification, and supplementation, all of which are used to combat vitamin A deficiency.[16] Toxicity is classified into two categories: acute and chronic. The former occurs a few hours or days after ingestion of a large amount of vitamin A. Chronic toxicity takes place when about 4,000 IU/kg or more of vitamin A is consumed for a long time. Symptoms of both include nausea, blurred vision, fatigue, weight-loss, and menstrual abnormalities.[17]
Excess vitamin A is 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; but excessive uptake of carotenoids can cause carotenosis.
Excess preformed vitamin A during early pregnancy is associated with a significant increase in birth defects.[18] These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects.[19] The FDA recommends that pregnant women get their vitamin A from foods containing beta carotene and that they 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 over-supplementation should be strictly avoided.
A review of all randomized controlled trials in the scientific literature by the
Studies emerging from developing countries India, Bangladesh, and Indonesia strongly suggest that, in populations in which vitamin A deficiency is common and maternal mortality is high, dosing expectant mothers can greatly reduce maternal mortality.[21] Similarly, dosing newborn infants with 50,000 IU (15 mg) of vitamin A within two days of birth can significantly reduce neonatal mortality.[22][23]
Biological roles
Retinol or other forms of vitamin A are needed for eyesight, maintenance of the skin, and human development.[1] Other than for vision, the active compound is all-trans-retinoic acid, synthesized from retinal, in turn synthesized from retinol.
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 to retinoic acid differently depending on the amount present. For example, in vertebrates, the hindbrain transiently forms eight
Stem cell biology
Retinoic acid is an influential factor used in differentiation 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 to posterior foregut lineages and also to functional motor neurons.
Vision
Retinol is an essential compound in the cycle of light-activated chemical reactions called the "
Without adequate amounts of retinol, regeneration of rhodopsin is incomplete and
Glycoprotein synthesis
Glycoprotein synthesis requires adequate vitamin A status. In severe vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.[26]
Immune system
Vitamin A is essential to maintain intact
Skin
Deficiencies in vitamin A have been linked to an increased susceptibility to skin infection and inflammation.
Red blood cells
Vitamin A may be needed for normal
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
Vitamin properties | |
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Solubility | Fat |
RDA (adult male)
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900 µg/day |
RDA (adult female) | 700 µg/day |
RDA upper limit (adult male) | 3,000 µg/day |
RDA upper limit (adult female) | 3,000 µg/day |
Deficiency symptoms | |
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Excess symptoms | |
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Common sources | |
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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 retinaldehyde 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 β-carotene. For this reason, amounts of vitamin A are measured in Retinol Equivalents (RE). One RE is equivalent to 0.001 mg of retinol, or 0.006 mg of β-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 consumed 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. National Health Service daily recommended values are slightly lower at 700 micrograms for men and 600 micrograms for women.[34]
During the absorption process in the
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.
Sources
Retinoids are found naturally only in foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75–7 oz (50–198 g):
Chemistry
Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a
Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating nuclear retinoic acid receptors.[24] 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.
Synthesis
Biosynthesis
Retinol is synthesized from the breakdown of
Industrial synthesis
Retinol is made industrially via
The world market for synthetic retinol is primarily for animal feed, leaving approximately 13% for a combination of food, prescription medication and dietary supplement use.
Production from natural β-carotene is possible, but is not industrially used.
History
In 1912, Frederick Gowland Hopkins demonstrated that unknown accessory factors found in milk, other than carbohydrates, proteins, and fats were necessary for growth in rats. Hopkins received a Nobel Prize for this discovery in 1929.[44] One year later, Elmer McCollum, a biochemist at the University of Wisconsin–Madison, and colleague Marguerite Davis identified a fat-soluble nutrient in butterfat and cod liver oil. Their work confirmed that of Thomas Burr Osborne and Lafayette Mendel, at Yale, also in 1913, which suggested a fat-soluble nutrient in butterfat.[45] The "accessory factors" were termed "fat soluble" in 1918 and later "vitamin A" in 1920. In 1931, Swiss chemist Paul Karrer described the chemical structure of vitamin A.[44] Retinoic acid and retinol were first synthesized in 1946 and 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.[46][47]
In 1967,
Although vitamin A was not confirmed as an essential nutrient and a chemical structure described until the 20th century, written observations of conditions created by deficiency of this nutrient appeared much earlier in history. Sommer 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 epidemiologic observations that identified the existence of this unique nutrient and manifestations of its deficiency.[21]
References
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- ^ a b c d "Office of Dietary Supplements - Vitamin A". ods.od.nih.gov. 31 August 2016. Archived from the original on 12 December 2016. Retrieved 30 December 2016.
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- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
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- ^ Nataraja A. "Man's best friend? (An account of Mertz's illness)". Archived from the original on 29 January 2007.
- ^ Gropper SS, Smith JL, Groff JL (2009). Advanced Nutrition and Human Metabolism (5th ed.). pp. 373–1182.
- ^ Thompson J, Manore M (2005). "Ch. 8: Nutrients involved in antioxidant function". Nutrition: An Applied Approach. Pearson Education Inc. pp. 276–283.
- ^ Mohsen SE, Mckinney K, Shanti MS (2008). "Vitamin A toxicity". Medscape. Archived from the original on 23 July 2013.
- ^ Challem J (1995). "Caution Urged With Vitamin A in Pregnancy: But Beta-Carotene is Safe". The Nutrition Reporter Newsletter. Archived from the original on 1 September 2004.
- ^ Stone B (6 October 1995). "Vitamin A and Birth Defects". United States FDA. Archived from the original on 4 February 2004.
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- ^ Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, et al. (2001). "Phototransduction". Neuroscience (2nd ed.). Sinauer Associates.
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- ^ "Vitamin A directs immune cells to intestines". ScienceDaily. Retrieved 17 March 2020.
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- ^ "Vitamin A and Skin Health". Linus Pauling Institute. 7 November 2016. Retrieved 10 August 2023.
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- ^ "Carotenoid Oxygenase". InterPro. Retrieved 7 November 2018.
- ^ "Vitamins and minerals - Vitamin A". nhs.uk. 23 October 2017. Retrieved 18 February 2023.
- ^ "Micronutrient deficiencies - Vitamin A deficiency". World Health Organization. 18 April 2018. Retrieved 18 April 2018.
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- ^ Brown JE (2002). Vitamins and Your Health. Nutrition Now (3rd ed.). pp. 1–20.
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- ^ DE 954247, Wittig G, Pommer H, "Verfahren zur Herstellung von best-Carotin bzw. 15,15'-Dehydro-beta-carotin", issued 13 December 1956.
- ^ US 2917524, Wittig G, Pommer H, "Compounds of the vitamin A series", issued 1959, assigned to Badische Anilin- & Soda-Fabrik Akt.-Ges.
- ^ US 2609396, Herloff IH, Horst P, "Compounds with the carbon skeleton of beta-carotene and process for the manufacture thereof", published 2 September 1952.
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External links
- Jane Higdon, "Vitamin A", Micronutrient Information Center, Linus Pauling Institute, Oregon State University
- NIH Office of Dietary Supplements – Vitamin A
- Vitamin A Deficiency at the Merck Manual of Diagnosis and Therapy