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Shabtai Y, Fainsod A (April 2018). "Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome". Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire. 96 (2): 148–160. doi: 10.1139/bcb-2017-0132. PMID 28982012. Fortunately, foods abundant in vitamin A are usually easy to come by and most are an excellent addition to a healthy diet. Cañete A, Cano E, Muñoz-Chápuli R, Carmona R (February 2017). "Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis". Nutrients. 9 (2): 159. doi: 10.3390/nu9020159. PMC 5331590. PMID 28230720.

Vitamin A deficiency (VAD) has been linked to compromised resistance to infectious diseases. [32] [33] In countries where early childhood VAD is common, vitamin A supplementation public health programs initiated in the 1980s were shown to reduce the incidence of diarrhea and measles, and all-cause mortality. [22] [34] [35] VAD also increases the risk of immune system over-reaction, leading to chronic inflammation in the intestinal system, stronger allergic reactions and autoimmune diseases. [32] [33] [36]a b c d Pino-Lagos K, Guo Y, Noelle RJ (2010). "Retinoic acid: a key player in immunity". BioFactors. 36 (6): 430–436. doi: 10.1002/biof.117. PMC 3826167. PMID 20803520. Tanumihardjo SA (August 2011). "Vitamin A: biomarkers of nutrition for development". The American Journal of Clinical Nutrition. 94 (2): 658S–665S. doi: 10.3945/ajcn.110.005777. PMC 3142734. PMID 21715511. There are causes for deficiency other than low dietary intake of vitamin A as retinol or carotenes. Adequate dietary protein and caloric energy are needed for a normal rate of synthesis of RBP, without which, retinol cannot be mobilized to leave the liver. Systemic infections can cause transient decreases in RBP synthesis even if protein-calorie malnutrition is absent. Chronic alcohol consumption reduces liver vitamin A storage. [4] Non-alcoholic fatty liver disease (NAFLD), characterized by the accumulation of fat in the liver, is the hepatic manifestation of metabolic syndrome. Liver damage from NAFLD reduces liver storage capacity for retinol and reduces the ability to mobilize liver stores to maintain normal circulating concentration. [75] Animal requirements [ edit ] Animal research (on mice), which is pre-clinical, also found Retinoid acid, the bioactive metabolite of vitamin A, to have an effect on brain areas responsible for memory and learning. [104] Cancer [ edit ]

According to a 2017 Cochrane review, vitamin A deficiency, using serum retinol less than 0.70µmol/L as a criterion, is a major public health problem affecting an estimated 190 million children under five years of age in low- and middle-income countries, primarily in Sub-Saharan Africa and Southeast Asia. In lieu of or in combination with food fortification programs, many countries have implemented public health programs in which children are periodically given very large oral doses of synthetic vitamin A, usually retinyl palmitate, as a means of preventing and treating VAD. Doses were 50,000 to 100,000 IU ( International units) for children aged 6 to 11 months and 100,000 to 200,000 IU for children aged 12 months to five years, the latter typically every four to six months. In addition to a 24% reduction in all-cause mortality, eye-related results were reported. Prevalence of Bitot's spots at follow-up were reduced by 58%, night blindness by 68%, xerophthalmia by 69%. [22] Gene regulation [ edit ] Vitamin A1, also known as retinol, is only found in animal-sourced foods, such as oily fish, liver, cheese, and butter. The capacity to store retinol in the liver means that well-nourished humans can go months on a vitamin A deficient diet without manifesting signs and symptoms of deficiency. Two liver cell types are responsible for storage and release: hepatocytes and hepatic stellate cells (HSCs). Hepatocytes take up the lipid-rich chylomicrons, bind retinol to retinol-binding protein 4 (RBP4), and transfer the retinol-RBP4 to HSCs for storage in lipid droplets as retinyl esters. Mobilization reverses the process: retinyl ester hydrolase releases free retinol which is transferred to hepatocytes, bound to RBP4, and put into blood circulation. Other than either after a meal or when consumption of large amounts exceeds liver storage capacity, more than 95% of retinol in circulation is bound to RBP4. [14] Carnivores [ edit ] Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought. As a result, in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids. [4] Substance and its chemical environment (per 1 μg) In addition to retinol, retinal and retinoic acid, there are plant-, fungi- or bacteria-sourced carotenoids which can be metabolized to retinol, and are thus vitamin A vitamers. [11]

What happens if I take too much vitamin E?

Filipinos soon to plant and eat Golden Rice". Philippine Rice Research Institute. 23 July 2021 . Retrieved 21 August 2021. a b "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. Archived (PDF) from the original on 28 August 2017. a b Bender DA (2003). Nutritional biochemistry of the vitamins. Cambridge, U.K.: Cambridge University Press. ISBN 978-0-521-80388-5. Pawlikowski B, Wragge J, Siegenthaler JA (July 2019). "Retinoic acid signaling in vascular development". Genesis. 57 (7–8): e23287. doi: 10.1002/dvg.23287. PMC 6684837. PMID 30801891. PRI Population Reference Intake is European Union equivalent of RDA; higher for adults than for children, and may be even higher for women who are pregnant or lactating. For Thiamin and Niacin the PRIs are expressed as amounts per MJ of calories consumed. MJ = megajoule = 239 food calories.

Carotenoid synthesis takes place in plants, certain fungi, and bacteria. Structurally carotenes are tetraterpenes, meaning that they are synthesized biochemically from four 10-carbon terpene units, which in turn were formed from eight 5-carbon isoprene units. Intermediate steps are the creation of a 40-carbon phytoene molecule, conversion to lycopene via desaturation, and then creation of ionone rings at both ends of the molecule. β-carotene has a β-ionone ring at both ends, meaning that the molecule can be divided symmetrically to yield two retinol molecules. α-Carotene has a β-ionone ring at one end and an Ɛ-ionone ring at the other, so it has half the retinol conversion capacity. [11] Vitamin A biosynthesis from β-carotene In 1931, Albert Szent-Györgyi and a fellow researcher Joseph Svirbely suspected that "hexuronic acid" was actually vitamin C, and gave a sample to Charles Glen King, who proved its activity counter to scurvy in his long-established guinea pig scorbutic assay. In 1937, Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943, Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery of vitamin K and its chemical structure. Omman RA, Kini AR (2020). "Leukocyte development, kinetics, and functions". In Keohane EM, Otto CN, Walenga JN (eds.). Rodak's Hematology: Clinical Principles and Applications (6thed.). St. Louis, Missouri: Elsevier. pp.117–35. ISBN 978-0-323-53045-3. Once discovered, vitamins were actively promoted in articles and advertisements in McCall's, Good Housekeeping, and other media outlets. [29] Marketers enthusiastically promoted cod-liver oil, a source of vitamin D, as "bottled sunshine", and bananas as a "natural vitality food". [40] They promoted foods such as yeast cakes, a source of B vitamins, on the basis of scientifically determined nutritional value, rather than taste or appearance. [40] In 1942, when flour enrichment with nicotinic acid began, a headline in the popular press said "Tobacco in Your Bread." In response, the Council on Foods and Nutrition of the American Medical Association approved of the Food and Nutrition Board's new names niacin and niacin amide for use primarily by non-scientists. It was thought appropriate to choose a name to dissociate nicotinic acid from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name niacin was derived from nicotinic acid + vitam in. [41] [42] Researchers also focused on the need to ensure adequate nutrition, especially to compensate for what was lost in the manufacture of processed foods. [29] Hardman, J.G.; etal., eds. (2001). Goodman and Gilman's Pharmacological Basis of Therapeutics (10thed.). McGraw-Hill. p.992. ISBN 978-0071354691.

These carotenoids include beta-carotene and alpha-carotene, which are collectively known as provitamin A. Herbivores consume ionone-containing carotenoids and convert those to retinal. Some species, including cattle and horses, have measurable amounts of beta-carotene circulating in the blood, and stored in body fat, creating yellow fat cells. Most species have white fat and no beta-carotene in circulation. [15] Activation and excretion [ edit ] You can easily meet your requirements for vitamin A by regularly eating some of the foods listed in this article. Many foods also contain added vitamin A, including cereals, margarine, and dairy products. For many years, a system of equivalencies in which an international unit (IU) was equal to 0.3 μg of retinol (~1nmol), 0.6 μg of β-carotene, or 1.2 μg of other provitamin-A carotenoids was used. [43] This relationship was alternatively expressed by the retinol equivalent (RE): one RE corresponded to 1 μg retinol, to 2 μg β-carotene dissolved in oil, to 6 μg β-carotene in foods, and to 12 μg of either α-carotene, γ-carotene, or β- cryptoxanthin in food. Al Nasser Y, Jamal Z, Albugeaey M (11 August 2021). "Carotenemia". StatPearls. Treasure Island (FL): StatPearls Publishing. doi: 10.1007/s00253-001-0902-7. PMID 30521299. S2CID 22232461.

a b c Wu L, Guo X, Wang W, Medeiros DM, Clarke SL, Lucas EA, etal. (November 2016). "Molecular aspects of β, β-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases". Experimental Biology and Medicine. 241 (17): 1879–1887. doi: 10.1177/1535370216657900. PMC 5068469. PMID 27390265. Niacin and Niacin Amide". Journal of the American Medical Association. 118 (10): 819. 7 March 1942. doi: 10.1001/jama.1942.02830100049011. Servallos NJ (20 April 2023). "SC issues writ vs GMO golden rice, eggplant". Philippine Star . Retrieved 22 September 2023. Zhao JG, Zeng XT, Wang J, Liu L (2017). "Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis". JAMA. 318 (24): 2466–2482. doi: 10.1001/jama.2017.19344. PMC 5820727. PMID 29279934. a b c Bono MR, Tejon G, Flores-Santibañez F, Fernandez D, Rosemblatt M, Sauma D (June 2016). "Retinoic Acid as a Modulator of T Cell Immunity". Nutrients. 8 (6): 349. doi: 10.3390/nu8060349. PMC 4924190. PMID 27304965.In 1930, Paul Karrer elucidated the correct structure for beta-carotene, the main precursor of vitamin A, and identified other carotenoids. Karrer and Norman Haworth confirmed Albert Szent-Györgyi's discovery of ascorbic acid and made significant contributions to the chemistry of flavins, which led to the identification of lactoflavin. For their investigations on carotenoids, flavins and vitamins A and B 2, they both received the Nobel Prize in Chemistry in 1937. [36] In setting human nutrient guidelines, government organizations do not necessarily agree on amounts needed to avoid deficiency or maximum amounts to avoid the risk of toxicity. [57] [11] [58] For example, for vitamin C, recommended intakes range from 40mg/day in India [63] to 155mg/day for the European Union. [64] The table below shows U.S. Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamins, PRIs for the European Union (same concept as RDAs), followed by what three government organizations deem to be the safe upper intake. RDAs are set higher than EARs to cover people with higher than average needs. Adequate Intakes (AIs) are set when there is not sufficient information to establish EARs and RDAs. Governments are slow to revise information of this nature. For the U.S. values, with the exception of calcium and vitamin D, all of the data date to 1997–2004. [65]