Editing Vitamin A (section)

====Retinol safety====
{{Main|Hypervitaminosis A}}

There are historical reports of acute hypervitaminosis from Arctic explorers consuming bearded seal or polar bear liver, both very rich sources of stored retinol,<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> and there are also case reports of acute hypervitaminosis from consuming fish liver,<ref>{{cite journal | vauthors = Schmitt C, Domangé B, Torrents R, de Haro L, Simon N | title = Hypervitaminosis A Following the Ingestion of Fish Liver: Report on 3 Cases from the Poison Control Center in Marseille | journal = Wilderness & Environmental Medicine | volume = 31 | issue = 4 | pages = 454–456 | date = December 2020 | pmid = 32861618 | doi = 10.1016/j.wem.2020.06.003 | s2cid = 221384282 | doi-access = free | title-link = doi }}</ref> but otherwise there is no risk from consuming too much via commonly consumed foods. Only consumption of retinol-containing dietary supplements can result in acute or chronic toxicity.<ref name=PKIN2020VitA/> Acute toxicity occurs after a single or short-term doses of greater than 150,000 μg. Symptoms include blurred vision, nausea, vomiting, dizziness and headache within 8 to 24 hours. For infants ages 0–6 months given an oral dose to prevent development of vitamin A deficiency, bulging skull fontanel was evident after 24 hours, usually resolved by 72 hours.<ref name="Imdad2016">{{cite journal | vauthors = Imdad A, Ahmed Z, Bhutta ZA | title = Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD007480 | date = September 2016 | pmid = 27681486 | pmc = 6457829 | doi = 10.1002/14651858.CD007480.pub3 }}</ref> Chronic toxicity may occur with long-term consumption of vitamin A at doses of 25,000–33,000 IU/day for several months.<ref name=lpi/> Excessive consumption of alcohol can lead to chronic toxicity at lower intakes.<ref name=ods/> Symptoms may include nervous system effects, liver abnormalities, [[fatigue]], muscle weakness, bone and skin changes and others. The adverse effects of both acute and chronic toxicity are reversed after consumption is stopped.<ref name="DRI VitA"/>

In 2001, for the purpose of determining ULs for adults, the US Institute of Medicine considered three primary adverse effects and settled on two: [[teratogen]]icity, i.e., causing birth defects, and liver abnormalities. Reduced bone mineral density was considered, but dismissed because the human evidence was contradictory.<ref name="DRI VitA"/> During pregnancy, especially during the first trimester, consumption of retinol in amounts exceeding 4,500 μg/day increased the risk of birth defects, but not below that amount, thus setting a "No-Observed Adverse-Effect Level" (NOAEL).{{Medical citation needed|date=December 2024}} Given the quality of the clinical trial evidence, the NOAEL was divided by an uncertainty factor of 1.5 to set the UL for women of reproductive age at 3,000 μg/day of preformed vitamin A.{{Medical citation needed|date=December 2024}} For all other adults, liver abnormalities were detected at intakes above 14,000 μg/day.{{Medical citation needed|date=December 2024}} Given the weak quality of the clinical evidence, an uncertainty factor of 5 was used, and with rounding, the UL was set at 3,000 μg/day.{{Citation needed|date=December 2024}}

For children, ULs were extrapolated from the adult value, adjusted for relative body weight. For infants, several case studies reported adverse effects that include bulging fontanels, increased intracranial pressure, loss of appetite, hyperirritability and skin peeling after chronic ingestion of the order of 6,000 or more μg/day. Given the small database, an uncertainty factor of 10 divided into the "Lowest-Observed-Adverse-Effect Level" (LOAEL) led to a UL of 600 μg/day.<ref name="DRI VitA"/>