Editing Vitamin A (section)

==Medical uses==

In 2022, vitamin A was the 346th most commonly prescribed medication in the United States, with more than 50,000 prescriptions.<ref>{{cite web | title = Vitamin A Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/VitaminA | access-date = 30 August 2024 }}</ref>

===Preventing and treating vitamin A deficiency===
{{Main|Vitamin A deficiency}}

Recognition of its prevalence and consequences has led to governments and non-government organizations promoting vitamin A fortification of foods<ref name=FortifMap/> and creating programs that administer large bolus-size oral doses of vitamin A to young children every four to six months.<ref name="Wirth2017"/> In 2008, the [[World Health Organization]] estimated that vitamin A supplementation over a decade in 40 countries averted 1.25 million deaths due to vitamin A deficiency.<ref>{{cite web |url=https://www.who.int/nutrition/topics/vad/en/index.html |title=Micronutrient Deficiencies – Vitamin A |access-date=9 April 2008 |publisher=World Health Organization |archive-url=https://web.archive.org/web/20110127030721/https://www.who.int/nutrition/topics/vad/en/index.html |archive-date=27 January 2011 |url-status=dead}}</ref> A Cochrane review reported that vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children ages six month to five years of age. All-cause mortality was reduced by 14%, and incidence of [[diarrhea]] by 12%.<ref name="Imdad2017">{{cite journal | vauthors = Imdad A, Mayo-Wilson E, Haykal MR, Regan A, Sidhu J, Smith A, Bhutta ZA | title = Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 11 | pages = CD008524 | date = March 2022 | pmid = 35294044 | pmc = 8925277 | doi = 10.1002/14651858.CD008524.pub4 }}</ref> However, a Cochrane review by the same group concluded there was insufficient evidence to recommend blanket vitamin A supplementation for infants one to six months of age, as it did not reduce infant mortality or morbidity.<ref name="Imdad2016"/>

=== Acne ===

==== Topical retinoic acid and retinol ====
[[File:Retinoids.svg|thumb|class=skin-invert-image|Retinoids: [[Tretinoin]] is ''all-trans''-retinoic acid; initial tradename: Retin-A. [[Isotretinoin]] is 13-''cis''-retinoic acid; initial tradename: Accutane. [[Etretinate]] and [[Acitretin]], its non-esterified metabolite, are used orally to treat severe [[psoriasis]].<ref name="Becken2015" />]]

Retinoic acids [[tretinoin]] (''all-trans''-retinoic acid) and [[isotretinoin]] (13-''cis''-retinoic acid) are prescription [[topical medication]]s used to treat moderate to severe cystic acne and acne not responsive to other treatments.<ref>{{cite web |date=22 March 2021 |title=Tretinoin |url=https://www.drugs.com/monograph/tretinoin.html |url-status=live |archive-url=https://web.archive.org/web/20161130124932/https://www.drugs.com/monograph/tretinoin.html |archive-date=30 November 2016 |access-date=23 December 2021 |publisher=The American Society of Health-System Pharmacists}}</ref><ref>{{cite journal |vauthors=Merritt B, Burkhart CN, Morrell DS |date=June 2009 |title=Use of isotretinoin for acne vulgaris |journal=Pediatric Annals |volume=38 |issue=6 |pages=311–320 |doi=10.3928/00904481-20090512-01 |pmid=19588674}}</ref><ref>{{cite journal |vauthors=Layton A |date=May 2009 |title=The use of isotretinoin in acne |journal=Dermato-Endocrinology |volume=1 |issue=3 |pages=162–169 |doi=10.4161/derm.1.3.9364 |pmc=2835909 |pmid=20436884}}</ref><ref name="Leyden2017">{{cite journal |vauthors=Leyden J, Stein-Gold L, Weiss J |date=September 2017 |title=Why Topical Retinoids Are Mainstay of Therapy for Acne |journal=Dermatology and Therapy |volume=7 |issue=3 |pages=293–304 |doi=10.1007/s13555-017-0185-2 |pmc=5574737 |pmid=28585191}}</ref> These are usually applied as a [[cream (pharmacy)|skin cream]] to the face after cleansing to remove make-up and skin oils. Tretinoin and isotretinoin act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR).<ref name="Kang S 2008">Kang S, Voorhees JJ. "Topical retinoids". In: ''Fitzpatrick's Dermatology in General Medicine'', 7th ed, Wolff K, Goldsmith LA, Katz SI, et al. (Eds), McGraw Hill, New York 2008. p. 2106.</ref> These events contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation.<ref>Fernandez EM, Zaenglein A, Thiboutot D. "Acne Treatment Methodologies". In: ''Cosmetic Formulation of Skin Care Products'', Taylor and Francis Group, New York 2006. p. 273.</ref> The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation.<ref name="Kang S 2008" /> Retinoic acid products also reduce [[sebum]] secretion, a nutrient source for bacteria, from facial pores.<ref>{{cite journal |vauthors=Khalil S, Bardawil T, Stephan C, Darwiche N, Abbas O, Kibbi AG, Nemer G, Kurban M |date=December 2017 |title=Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects |journal=The Journal of Dermatological Treatment |volume=28 |issue=8 |pages=684–696 |doi=10.1080/09546634.2017.1309349 |pmid=28318351}}</ref>

These drugs, when applied topically, are US-designated Pregnancy Category C (animal reproduction studies have shown an adverse effect on the fetus), and should not be used by pregnant women or women who are anticipating becoming pregnant.<ref name="Tretinoin" /> Many countries established a physician- and patient- education pregnancy prevention policy.<ref>{{cite journal |vauthors=Kovitwanichkanont T, Driscoll T |date=September 2018 |title=A comparative review of the isotretinoin pregnancy risk management programs across four continents |journal=International Journal of Dermatology |volume=57 |issue=9 |pages=1035–1046 |doi=10.1111/ijd.13950 |pmid=29508918 |s2cid=3726217}}</ref>

[[Trifarotene]] is a prescription retinoid for the topical treatment acne vulgaris.<ref name="Monograph" /> It functions as a [[Retinoic acid receptor gamma|retinoic acid receptor (RAR)-γ]] [[agonist]].<ref name="Scott2019">{{cite journal |vauthors=Scott LJ |date=November 2019 |title=Trifarotene: First Approval |journal=Drugs |volume=79 |issue=17 |pages=1905–1909 |doi=10.1007/s40265-019-01218-6 |pmid=31713811 |s2cid=207964653}}</ref>

Non-prescription [[cream (pharmacy)|topical products]] that have health claims for reducing facial acne, combating skin dark spots and reducing wrinkles and lines associated with aging often contain [[retinyl palmitate]]. The hypothesis is that this is absorbed and de-esterified to free retinol, then converted to retinaldehyde and further metabolized to ''all-trans''-retinoic acid, whence it will have the same effects as prescription products with fewer side effects.<ref>{{cite journal |vauthors=Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G |date=2006 |title=Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety |journal=Clinical Interventions in Aging |volume=1 |issue=4 |pages=327–348 |doi=10.2147/ciia.2006.1.4.327 |pmc=2699641 |pmid=18046911 |doi-access=free |title-link=doi}}</ref> There is some ''ex vivo'' evidence with human skin that esterified retinol is absorbed and then converted to retinol.<ref>{{cite journal |vauthors=Boehnlein J, Sakr A, Lichtin JL, Bronaugh RL |date=August 1994 |title=Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retinol (vitamin A) during percutaneous absorption |journal=Pharmaceutical Research |volume=11 |issue=8 |pages=1155–1159 |doi=10.1023/A:1018941016563 |pmid=7971717 |s2cid=25458156}}</ref> In addition to esterified retinol, some of these products contain hydroxypinacolone retinoate, identified as esterified 9-''cis''-retinoic acid.<ref>{{cite journal |vauthors=Villani A, Annunziata MC, Cinelli E, Donnarumma M, Milani M, Fabbrocini G |date=October 2020 |title=Efficacy and safety of a new topical gel formulation containing retinol encapsulated in glycospheres and hydroxypinacolone retinoate, an antimicrobial peptide, salicylic acid, glycolic acid and niacinamide for the treatment of mild acne: preliminary results of a 2-month prospective study |journal=Giornale Italiano di Dermatologia e Venereologia |volume=155 |issue=5 |pages=676–679 |doi=10.23736/S0392-0488.20.06581-5 |pmid=32869963 |s2cid=221402891}}</ref>

==== Oral isotretinoin ====
Oral [[isotretinoin]] (retinoic acid [[isomer]]) is recommended for treating treatment resistant [[acne]], acne that can lead to scarring, and acne that is associated with psychosocial distress.<ref name="Reynolds_2024">{{cite journal | vauthors = Reynolds RV, Yeung H, Cheng CE, Cook-Bolden F, Desai SR, Druby KM, Freeman EE, Keri JE, Stein Gold LF, Tan JK, Tollefson MM, Weiss JS, Wu PA, Zaenglein AL, Han JM, Barbieri JS | title = Guidelines of care for the management of acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 90 | issue = 5 | pages = 1006.e1–1006.e30 | date = May 2024 | pmid = 38300170 | doi = 10.1016/j.jaad.2023.12.017 }}</ref> It is approved by the FDA for treating severe acne vulgaris that is resistant to other treatment options.<ref name="Reynolds_2024" /> Isotretinoin is a known teratogen, with an estimated 20–35% risk of physical birth defects to infants that are exposed to isotretinoin ''in utero'', including numerous congenital defects such as craniofacial defects, cardiovascular and neurological malformations or thymic disorders.<ref name="Draghici2021" /> Neurocognitive impairments in the absence of any physical defects has been established to be 30–60%.<ref name="Draghici2021" /> For these reasons, physician- and patient-education programs were initiated, recommending that for women of child-bearing age, contraception be initiated a month before starting oral (or topical) isotretinoin, and continue for a month after treatment ended.<ref name="Draghici2021"/> In the US, isotretinoin was released to the market in 1982 as a revolutionary treatment for severe and refractory [[acne vulgaris]]. It was shown that a dose of 0.5–1.0&nbsp;mg/kg body weight/day is enough to produce a reduction in sebum excretion by 90% within a month or two, but the recommended treatment duration is 4 to 6 months.<ref name="Draghici2021" />

The mechanism by which orally consumed retinoic acid (RA), as ''all-trans''-tretinoin or 13-''cis''-isotretinoin improves facial skin health is thought to be by switching on genes and differentiating keratinocytes (immature skin cells) into mature epidermal cells.<ref name="Reynolds_2024" /> RA reduces the size and secretion of the sebaceous glands, and by doing so reduces bacterial numbers in both the ducts and skin surface.<ref name="Reynolds_2024" /> It reduces inflammation via inhibition of chemotactic responses of monocytes and neutrophils.  

=== Other dermatological conditions ===
In addition to the approved use for treating acne vulgaris, researchers have investigated off-label applications for dermatological conditions, such as rosacea, psoriasis, and other conditions.<ref name="Nickle2014">{{cite journal | vauthors = Nickle SB, Peterson N, Peterson M | title = Updated Physician's Guide to the Off-label Uses of Oral Isotretinoin | journal = The Journal of Clinical and Aesthetic Dermatology | volume = 7 | issue = 4 | pages = 22–34 | date = April 2014 | pmid = 24765227 | pmc = 3990537 | doi = }}</ref> [[Rosacea]] was reported as responding favorably to doses lower than used for acne. Isotretinoin in combination with ultraviolet light was shown affective for treating [[psoriasis]]. Isotretinoin in combination with injected [[interferon-alpha]] showed some potential for treating [[genital warts]]. Isotretinoin in combination with topical [[fluorouracil]] or injected interferon-alpha showed some potential for treating precancerous skin lesions and skin cancer.<ref name="Nickle2014"/>

=== Immune function ===
Vitamin A plays an important role in the body's immune function, both the adaptive response, and to help the body fight off infection.<ref name="Cheng_2024">{{cite journal | vauthors = Cheng X, Li D, Yang C, Chen B, Xu P, Zhang L | title = Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age | journal = The Cochrane Database of Systematic Reviews | volume = 2024 | issue = 5 | pages = CD015306 | date = May 2024 | pmid = 38738639 | pmc = 11089595 | doi = 10.1002/14651858.CD015306.pub2 }}</ref> The anti-inflammatory effects of vitamin A also contribute to repairing mucosal cells that can be damaged by an infection.<ref name="Cheng_2024" /> For these reasons, there have been quite a few studies looking at the potential role that Vitamin A supplementation may play in improving an immune response or to helping the body fight off an infection. The evidence supporting vitamin A supplementation for children under the age of 7 years to prevent upper respiratory tract infections is weak, and the weak evidence from low-quality clinical trials does not support vitamin A as being effective or having a benefit.<ref name="Cheng_2024" /> More research is needed to consider different doses, the ages and populations of people who may potentially benefit, and the length of treatment.<ref name="Cheng_2024" />