Editing Retinol (section)

==Side effects==<!-- This section is linked from [[Cod liver oil]] -->
{{see also|Hypervitaminosis A}}
The [[Dietary Reference Intake|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.<ref name=ods/> In pregnancy, the vitamin A RDA is 750–770 RAE/day (about 2,500–2,550 IU).<ref name=ods/> During [[lactation]], the RDA increases to 1,200–1,300 RAE/day (about 4,000–4,300 IU, with differences depending on age).<ref name=ods/> 

Retinol Activity Units can only be converted to IU (International Units) when the source of the vitamin A is known.<ref name=ods/> The IU values listed above do not apply to food sources of vitamin A.<ref name="ods">{{cite web|url=https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/|title=Vitamin A: Fact Sheet for Health Professionals |date=15 December 2023|publisher=Office of Dietary Supplements, National Institutes of Health|accessdate=10 September 2024}}</ref>

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,<ref>{{cite journal | vauthors = Rodahl K, Moore T | title = The vitamin A content and toxicity of bear and seal liver | journal = The Biochemical Journal | volume = 37 | issue = 2 | pages = 166–168 | date = July 1943 | pmid = 16747610 | pmc = 1257872 | doi = 10.1042/bj0370166 }}</ref> 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 [[Switzerland|Swiss]] scientist, who died in January 1913 on an [[Antarctica|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.<ref>{{cite web | vauthors = Nataraja A |title=Man's best friend? (An account of Mertz's illness) |url= http://www.studentbmj.com/back_issues/0502/life/158.html|archive-url= https://web.archive.org/web/20070129213607/http://www.studentbmj.com/back_issues/0502/life/158.html |archive-date=29 January 2007 }}</ref>

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.<ref name=Gropper>{{cite book | vauthors = Gropper SS, Smith JL, Groff JL | date = 2009 | title = Advanced Nutrition and Human Metabolism | edition = 5th | pages = 373–1182 }}</ref> 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.<ref>{{cite book | vauthors = Thompson J, Manore M | date = 2005| chapter = Ch. 8: Nutrients involved in antioxidant function | pages = 276–283 | title = Nutrition: An Applied Approach | publisher = Pearson Education Inc. }}</ref> 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.<ref>{{cite journal | vauthors = Mohsen SE, Mckinney K, Shanti MS | date = 2008 | url = http://emedicine.medscape.com/article/819426-overview | title = Vitamin A toxicity | archive-url = https://web.archive.org/web/20130723040000/http://emedicine.medscape.com/article/819426-overview | archive-date = 23 July 2013 | url-status = live | journal = Medscape }}</ref>

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 or retinyl esters into vitamin A is downregulated when physiological requirements are met;<ref>{{cite journal | vauthors = Steinhoff JS, Wagner C, Dähnhardt HE, Košić K, Meng Y, Taschler U, Pajed L, Yang N, Wulff S, Kiefer MF, Petricek KM, Flores RE, Li C, Dittrich S, Sommerfeld M, Guillou H, Henze A, Raila J, Wowro SJ, Schoiswohl G, Lass A, Schupp M | title = Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting | journal = EMBO Reports | volume = 25 | issue = 7 | pages = 2878–2895 | date = July 2024 | pmid = 38769419 | pmc = 11239848 | doi = 10.1038/s44319-024-00158-x }}</ref> but excessive uptake of carotenoids can cause [[carotenosis]].

Excess preformed vitamin A during early pregnancy is associated with a significant increase in birth defects.<ref>{{cite web| vauthors = Challem J |title=Caution Urged With Vitamin A in Pregnancy: But Beta-Carotene is Safe|url=http://www.thenutritionreporter.com/A-vitamins.html|website=The Nutrition Reporter Newsletter|archive-url=https://web.archive.org/web/20040901090549/http://www.thenutritionreporter.com/A-vitamins.html|archive-date=1 September 2004|date=1995}}</ref> These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects.<ref>{{cite web| vauthors = Stone B |title=Vitamin A and Birth Defects|url=https://www.fda.gov/bbs/topics/ANSWERS/ANS00689.html|publisher=United States FDA|archive-url=https://web.archive.org/web/20040204082441/https://www.fda.gov/bbs/topics/ANSWERS/ANS00689.html|archive-date=4 February 2004|date=6 October 1995}}</ref> 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 sufficient stores of vitamin A in their liver cells,<ref>{{cite journal | vauthors = Steinhoff JS, Wagner C, Dähnhardt HE, Košić K, Meng Y, Taschler U, Pajed L, Yang N, Wulff S, Kiefer MF, Petricek KM, Flores RE, Li C, Dittrich S, Sommerfeld M, Guillou H, Henze A, Raila J, Wowro SJ, Schoiswohl G, Lass A, Schupp M | title = Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting | journal = EMBO Reports | volume = 25 | issue = 7 | pages = 2878–2895 | date = July 2024 | pmid = 38769419 | pmc = 11239848 | doi = 10.1038/s44319-024-00158-x }}</ref> so over-supplementation should be strictly avoided.

A review of all randomized controlled trials in the scientific literature by the [[Cochrane Collaboration]] published in ''[[Journal of the American Medical Association|JAMA]]'' in 2007 found that supplementation with beta carotene or vitamin A ''increased'' mortality by 5% and 16%, respectively.<ref>{{cite journal | vauthors = Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C | title = Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis | journal = JAMA | volume = 297 | issue = 8 | pages = 842–857 | date = February 2007 | pmid = 17327526 | doi = 10.1001/jama.297.8.842 | url = http://dcscience.net/bjelakovic-supplements-07.pdf | url-status = live | archive-url = https://web.archive.org/web/20160204172729/http://dcscience.net/bjelakovic-supplements-07.pdf | archive-date = 4 February 2016 }}</ref> This effect has been attributed to the role of retinol and retinoic acid in increasing circulating cholesterol and triglycerides as well as promoting cancer incidence.<ref>{{cite journal | vauthors = Esposito M, Amory JK, Kang Y | title = The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes | journal = The Journal of Experimental Medicine | volume = 221 | issue = 9 | date = September 2024 | pmid = 39133222 | doi = 10.1084/jem.20240519 | doi-access = free | pmc = 11318670 }}</ref>

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 with retinol can greatly reduce maternal mortality.<ref name=Sommer>{{cite journal | vauthors = Sommer A | title = Vitamin a deficiency and clinical disease: an historical overview | journal = The Journal of Nutrition | volume = 138 | issue = 10 | pages = 1835–1839 | date = October 2008 | pmid = 18806089 | doi = 10.1093/jn/138.10.1835 | doi-access = free }}</ref> Similarly, dosing newborn infants with 50,000 IU (15&nbsp;mg) of vitamin A within two days of birth can significantly reduce neonatal mortality.<ref>{{cite journal | vauthors = Tielsch JM, Rahmathullah L, Thulasiraj RD, Katz J, Coles C, Sheeladevi S, John R, Prakash K | title = Newborn vitamin A dosing reduces the case fatality but not incidence of common childhood morbidities in South India | journal = The Journal of Nutrition | volume = 137 | issue = 11 | pages = 2470–2474 | date = November 2007 | pmid = 17951487 | doi = 10.1093/jn/137.11.2470 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Klemm RD, Labrique AB, Christian P, Rashid M, Shamim AA, Katz J, Sommer A, West KP | title = Newborn vitamin A supplementation reduced infant mortality in rural Bangladesh | journal = Pediatrics | volume = 122 | issue = 1 | pages = e242–e250 | date = July 2008 | pmid = 18595969 | doi = 10.1542/peds.2007-3448 | s2cid = 27427577 }}</ref>