Vitamin A
54114
225975093
2008-07-16T08:00:47Z
133.67.203.167
/* Vision */
[[Image:Retinol structure.svg|right|thumb|360px|The structure of retinol, the most common dietary form of vitamin A]]
'''Vitamin A''' is an essential human nutrient. Vitamin A actually refers to a family of similarly shaped molecules: the [[retinoids]]. Its important part is the retinyl group, which can be found in several forms. In foods of animal origin, the major form of vitamin A is an [[ester]], primarily [[retinyl palmitate]], which is converted to an [[alcohol]] ([[retinol]]) in the small intestine. Vitamin A can also exist as an [[aldehyde]] ([[retinal]]), or as an acid ([[retinoic acid]]). Precursors to the vitamin ([[provitamin]]s) are present in foods of plant origin as some of the members of the [[carotenoid]] family of compounds.<ref name="encyclo"> Carolyn Berdanier. 1997. Advanced Nutrition Micronutrients. pp 22-39</ref>
All forms of vitamin A have a [[Ionone|Beta-ionone]] ring to which an [[Isoprene|isoprenoid]] chain is attached. This structure is essential for vitamin activity.<ref name="encyclo"/> The orange pigment of [[carrot]] - [[Beta-carotene]] - can be represented as two connected retinyl groups. The retinyl group, when attached to a specific protein, is the only primary light absorber in [[visual perception]], and the compound name is related to the [[retina]] of the eye.
Vitamin A can be found in various forms:
*[[retinol]], the form of vitamin A absorbed when eating animal food sources, is a yellow, fat-soluble, [[vitamin]] with importance in vision and bone growth. Since the alcohol form is unstable, the vitamin is usually produced and administered in a form of retinyl [[acetate]] or [[palmitate]].
*other [[retinoid]]s, a class of chemical compounds that are related chemically to vitamin A, are used in medicine.<ref> [http://www.cancer.org/docroot/CRI/content/CRI_2_4_4x_Retinoid_Therapy.asp?sitearea= American Cancer Society: Retinoid Therapy]</ref>
==Discovery of vitamin A==
The discovery of vitamin A stemmed from research dating back to [[1906]], indicating that factors other than [[carbohydrate]]s, [[protein]]s, and [[fat]]s were necessary to keep [[cattle]] healthy.<ref name="Discovery"> {{cite journal|title=Discovery of Vitamin A|journal=Encyclopedia of Life Sciences|date=2001-04-19|first=George|last=Wolf|coauthors=|volume=|issue=|pages=|doi= 10.1038/npg.els.0003419|url=http://www.mrw.interscience.wiley.com/emrw/9780470015902/els/article/a0003419/current/html|format=|accessdate=2007-07-21}}</ref> By [[1917]] one of these substances was independently discovered by [[Elmer McCollum]] at the [[University of Wisconsin-Madison]], and [[Lafayette Mendel]] and Thomas Osborne at [[Yale University]]. Since "water-[[soluble]] factor B" ([[Vitamin B]]) had recently been discovered, the researchers chose the name "fat-soluble factor A" ('''vitamin A''').<ref name="Discovery" /> Vitamin A was first synthesized in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.
== Equivalencies of retinoids and carotenoids (IU) ==
Since some carotenoids can be converted into vitamin A, attempts have been made to determine how much of them in the diet is equivalent to a particular amount of retinol, so that comparisons can be made of the benefit of different foods. Unfortunately the situation is confusing because the accepted equivalences have changed. For many years, a system of equivalencies was used in which an [[international unit]] (IU) was equal to 0.3 micrograms of retinol, 0.6 [[microgram|μg]] of β-carotene, or 1.2 μg of other provitamin-A carotenoids.<ref>
''[http://www.nal.usda.gov/fnic/foodcomp/Data/SR20/SR20_doc.pdf Composition of Foods Raw, Processed, Prepared USDA National Nutrient Database for Standard Reference, Release 20]'' [[USDA]], Feb. 2008</ref> Later, a unit called [[retinol equivalent]] (RE) was introduced. 1 RE corresponded to 1 μg retinol, 2 μg β-carotene dissolved in oil (as in supplement pills), 6 μg β-carotene in normal food (because it is not absorbed as well as from supplements), and 12 μg of either [[α-carotene]] or [[β-cryptoxanthin]] in food.
However, new research showed that the absorption of provitamin-A carotenoids was only half as much as previously thought, so in 2001 the US [[Institute of Medicine]] recommended a new unit, the [[retinol activity equivalent]] (RAE). 1 μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of other dietary provitamin-A carotenoids.<ref name=Chapter4>[http://www.nal.usda.gov/fnic/DRI//DRI_Vitamin_A/82-161_150.pdf Chapter 4, Vitamin A] of [http://fnic.nal.usda.gov/nal_display/index.php?info_center=4&tax_level=4&tax_subject=256&topic_id=1342&level3_id=5141&level4_id=10590 Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, hickel, Silicon, Vanadium, and Zinc], [[Food and Nutrition Board]] of the [[Institute of Medicine]], 2001</ref>
{| class="prettytable"
|-
! Substance and its chemical environment
! Micrograms of retinol equivalent per microgram of the substance
|-
| retinol
|align="right"| 1
|-
| [[beta-carotene]], dissolved in oil
|align="right"| 1/2
|-
| beta-carotene, common dietary
|align="right"| 1/12
|-
| alpha-carotene, common dietary
|align="right"| 1/24
|-
| beta-cryptoxanthin, common dietary
|align="right"| 1/24
|}
Because the production of retinol from provitamins by the human body is regulated by the amount of retinol available to the body, the conversions apply strictly only for vitamin A deficient humans. The absorption of provitamins also depends greatly on the amount of lipids ingested with the provitamin; lipids increase the uptake of the provitamin.<ref>NW Solomons, M Orozco.
''[http://www.healthyeatingclub.org/APJCN/volume12/vol12.3/fullArticles/SolomonsVit.pdf Alleviation of Vitamin A deficiency with palm fruit and its products]''. Asia Pac J Clin Nutr, 2003</ref>
The conclusion that can be drawn from the newer research is that fruits and vegetables are not as useful for obtaining vitamin A as was thought--in other words, the IU's that they were reported to contain were worth much less than the same number of IU's of fat-dissolved supplements. This is important for [[vegetarian]]s. ([[Night blindness]] is prevalent in countries where little meat or vitamin A-fortified foods are available.) A sample [[vegan]] diet for one day that provides sufficient vitamin A has been published by the Food and Nutrition Board (page 120<ref name=Chapter4/>). On the other hand, reference values for retinol or its equivalents, provided by the [[United States National Academy of Sciences|National Academy of Sciences]], have decreased. The [[recommended daily allowance|RDA]] (for men) of 1968 was 5000 IU (1500 μg retinol). In 1974 the RDA was set to 1000 RE (1000 μg retinol), whereas now the [[Dietary Reference Intake]] is 900 RAE (900 μg or 3000 IU retinol). This is equivalent to 1800 μg of β-carotene supplement (3000 IU) or 10800 μg of β-carotene in food (18000 IU).
==Recommended daily intake==
'''Vitamin A''' <br />[[Dietary Reference Intake]]:
{| class="wikitable"
|-
! Life Stage Group
! '''RDA'''/AI*
ug/day
! UL
ug/day
|-
| '''Infants'''
0-6 months<br />7-12 months
| <br />400*<br />500*
| <br />600<br />600
|-
| '''Children'''
1-3 years<br />4-8 years
| <br />300<br />400
| <br />600<br />900
|-
| '''Males'''
9-13 years<br />14-18 years<br />19 - >70 years
| <br />600<br />900<br />900
| <br />1700<br />2800<br />3000
|-
| '''Females'''
9-13 years<br />14-18 years<br />19 - >70 years
| <br />600<br />700<br />700
| <br />1700<br />2800<br />3000
|-
| '''Pregnancy'''
<19 years<br />19 - >50 years
| <br />750<br />770
| <br />2800<br />3000
|-
| '''Lactation'''
<19 years<br />19 - >50 years
| <br />1200<br />1300
| <br />2800<br />3000
|}
RDA = Recommended Dietary Allowances<br />
AI* = Adequate Intakes<br />
UL = Upper Limit<br />
(Note that the limit refers to [[retinoid]] forms of vitamin A. [[Carotene]] forms from [[dietary]] sources are not [[toxic]].<ref>{{cite web|url=http://www.vitamins-supplements.org/vitamin-A-sources.php|title=Sources of vitamin A|accessdate=2007-08-27}}</ref>)
According to the Institute of Medicine of the National Academies, "RDAs are set to meet the needs of almost all (97 to 98 percent) individuals in a group. For healthy breastfed infants, the AI is the mean intake. The AI for other life stage and gender groups is believed to cover the needs of all individuals in the group, but lack of data prevent being able to specify with confidence the percentage of individuals covered by this intake."<ref>Food and Nutrition Board. Institute of Medicine. National Academies. (2001) "Dietary Reference Intakes"</ref>
[http://www.iom.edu/Object.File/Master/7/296/webtablevitamins.pdf]
==Sources of Vitamin A==
Vitamin A is found naturally in many foods:
<div style="-moz-column-count:2; column-count:2;">
*'''[[liver]] (beef, pork, chicken, turkey, fish)''' (6500 μg 722%)
*'''[[carrots]]''' (835 μg 93%)
*'''[[Broccoli|Broccoli leaves]]''' (800 μg 89%) - Acc. to [http://www.nal.usda.gov/fnic/foodcomp/search/ USDA database]. Broccoli florets supposedly have much less - see note<ref>The RAE value in the USDA data for broccoli leaves is similar to the IU value for broccoli florets, which implies rather improbably that the leaves have about 20 times as much beta-carotene. It is possible that there was an error in the table.<!--This is not "original research"! I could just put a {{verify credibility}} tag on this, but I thought it would be better to specify why it seems incredible. If you think the value of 800 μg is good, let's discuss it on the talk page. --></ref>.
*'''[[sweet potatoes]]''' (709 μg 79%)
*'''[[kale]]''' (681 μg 76%)
*'''[[butter]]''' (684 μg 76%)
*'''[[spinach]]''' (469 μg 52%)
*[[leafy vegetables]]
*'''[[pumpkin]]''' (369 μg 41%)
*'''[[collard greens]]''' (333 μg 37%)
*'''[[cantaloupe melon]]''' (169 μg 19%)
*[[egg (food)|eggs]] (140 μg 16%)
*[[apricots]] (96 μg 11%)
*[[papaya]] (55 μg 6%)
*[[mango]] (38 μg 4%)
*[[peas]] (38 μg 4%)
*[[broccoli]] (31 μg 3%)
*[[winter squash]]
</div>
Note: bracketed values are retinol equivalences and percentage of the adult male [[Recommended Dietary Allowance|RDA]] per 100g.
Conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies.<ref>{{cite journal |author=Borel P, Drai J, Faure H, ''et al'' |title=[Recent knowledge about intestinal absorption and cleavage of carotenoids] |language=French |journal=Ann. Biol. Clin. (Paris) |volume=63 |issue=2 |pages=165–77 |year=2005 |pmid=15771974 |doi=}}</ref><ref>{{cite journal |author=Tang G, Qin J, Dolnikowski GG, Russell RM, Grusak MA |title=Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables |journal=Am. J. Clin. Nutr. |volume=82 |issue=4 |pages=821–8 |year=2005 |pmid=16210712 |doi=}}</ref>
==Metabolic Functions of Vitamin A==
Vitamin A plays a role in a variety of functions throughout the body, such as:
* Vision
* Gene Transcription
* Immune Function
* Embryonic Development and Reproduction
* Bone Metabolism
* Haematopoiesis
* Skin Health
* Reducing Risk of Heart Disease and Cancer
* Antioxidant Activity
===Vision===
The role of vitamin A in the vision cycle is specifically related to the retinal form. Within the eye, 11-''cis''-retinal is bound to rhodopsin (rods) and iodopsin (cones) at conserved lysine residues. As light enters the eye the 11-''cis''-retinal is isomerized to the all-"trans" form. The all-"trans" retinal dissociates from the opsin in a series of steps called bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. Upon completion of this cycle, the all-"trans"-retinal can be recycled and converted back to the 11-"cis"-retinal form via a series of enzymatic reactions. Additionally, some of the all-"trans" retinal may be converted to all-"trans" retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-"trans" retinyl esters allow this final form to be stored within the pigment epithelial cells to be reused when needed.<ref name="Combs2008" /> The final conversion of 11-''cis''-retinal will rebind to opsin to reform rhodopsin in the retina. Rhodopsin is needed to see black and white as well as see at night. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin and lead to night blindness.<ref name="McGuire2007">{{cite book |title=Nutritional sciences: from fundamentals to food |last=McGuire |first=Michelle |authorlink= |coauthors=Beerman, Kathy A. |year=2007 |publisher=Thomson/Wadsworth |location=Belmont, CA |isbn=0534537170 |pages= }}</ref>
===Gene Transcription===
Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (by retinol dehydrogenases) and then retinal can be oxidized to retinoic acid (by retinal oxidase). The conversion of retinal to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors.<ref name="Combs2008" /> Retinoic acid can bind to two different nuclear receptors to initiate (or inhibit) gene transcription: the retinoic acid receptors (RARs) or the retinoid "X" receptors (RXRs). RAR and RXR must dimerize before they can bind to the DNA. RAR will form a heterodimer with RXR (RAR-RXR), but it does not readily form a homodimer (RAR-RAR). RXR, on the other hand, readily forms a homodimer (RXR-RXR) and will form heterodimers with many other nuclear receptors as well, including the thyroid hormone receptor (RXR-TR), the Vitamin D<sub>3</sub> receptor (RXR-VDR), the peroxisome proliferator-activated receptor (RXR-PPAR) and the liver "X" receptor (RXR-LXR).<ref name="Stipanuk2006">{{cite book |title=Biochemical, Physiological and Molecular Aspects of Human Nutrition |last=Stipanuk |first=Martha H. |authorlink= |coauthors= |year=2006 |edition=2nd edition |publisher=Saunders |location=Philadelphia |isbn=978116002093 |pages= }}</ref> The RAR-RXR heterodimer recognizes retinoid acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid "X" response elements (RXREs) on the DNA. The other RXR heterodimers will bind to various other response elements on the DNA.<ref name="Combs2008" /> Once the retinoic acid binds to the receptors and dimerization has occurred, the receptors undergo a conformational change that causes co-repressors to dissociate from the receptors. Coactivators can then bind to the receptor complex, which may help to loosen the chromatin structure from the histones or may interact with the transcriptional machinery.<ref name="Stipanuk2006" /> The receptors can then bind to the response elements on the DNA and upregulate (or downregulate) the expression of target genes, such as cellular retinol-binding protein (CRBP) as well as the genes that encode for the receptors themselves.<ref name="Combs2008" />
===Dermatology===
Vitamin A appears to function in maintaining normal skin health. The mechanisms behind retinoid's therapeutic agents in the treatment of dermatological diseases are being researched. For the treatment of acne, the most effective drug is 13-cis retinoic acid (isotretinoin). Although its mechanism of action remains unknown, it is the only retinoid that dramatically reduces the size and secretion of the sebaceous glands. isotretinoin reduces bacterial numbers in both the ducts and skin surface. This is thought to be a result of the reduction in sebum, a nutrient source for the bacteria. Isotretinoin reduces inflammation via inhibition of chemotatic responses of monocytes and neutrophils.<ref name="Combs2008" /> Isotretinoin also has been shown to initiate remodeling of the sebaceous glands; triggering changes in gene expression that selectively induces apoptosis.<ref name="Nelson2008">{{ cite journal | last = Nelson | first = A. M. | authorlink = | coauthors = ''et al.'' | year = 2008 | month = | title = Neutrophil gelatinase-associated lipocalin mediates 13-''cis'' retinoic acid-induced apoptosis of human sebaceous gland cells | journal = Journal of Clinical Investigation | volume = 118 | issue = 4 | pages = 1468–1478 | doi = 10.1172/JCI33869 | url = | accessdate = | quote = }}</ref> Isotretinoin is a teratogen and its use is confined to medical supervision.
==Deficiency==
Vitamin A deficiency is estimated to affect millions of children around the world. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa.<ref>{{cite web |url=http://www.dietary-supplements.info.nih.gov/factsheets/vitamina.asp |title=Office of Dietary Supplements. Vitamin A |accessdate=2008-04-08 |format= |work=National Institute of Health }}</ref> According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern. With the high prevalence of vitamin A deficiency, the WHO has implemented several initiatives for supplementation of vitamin A in developing countries. Some of these strategies include intake of vitamin A through a combination of breast feeding, dietary intake, food fortification, and supplementation. Through the efforts of WHO and its partners, an estimated 1.25 million deaths since 1998 in 40 countries due to vitamin A deficiency have been averted.<ref>{{cite web |url=http://www.who.int/nutrition/topics/vad/en/index.html |title=Micronutrient Deficiencies-Vitamin A |accessdate=2008-04-09 |format= |work=World Health Organization }}</ref>
Vitamin A deficiency can occur as either a primary or secondary deficiency. A primary vitamin A deficiency occurs among children and adults who do not consume an adequate intake of yellow and green vegetables, fruits and liver. Early weaning can also increase the risk of vitamin A deficiency. Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, low fat diets, and chronic exposure to oxidants, such as cigarette smoke. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor utilization of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and the oxidation of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the risk of vitamin A deficiency and lead to several physiological events.<ref name="Combs2008" /> A study in [[Burkina Faso]] showed major reduction of malaria morbidity with combined vitamin A and [[zinc]] supplementation in young children.<ref name="pmid18237394">{{cite journal |author=Zeba AN, Sorgho H, Rouamba N, ''et al'' |title=Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial |journal=Nutr J |volume=7 |issue= |pages=7 |year=2008 |pmid=18237394 |doi=10.1186/1475-2891-7-7 |url=http://www.nutritionj.com/content/7/1/7}}</ref>
Since the unique function of retinyl group is the light absorption in [[Retinylidene protein]], one of the earliest and specific manifestations of [[vitamin A deficiency]] is impaired vision, particularly in reduced light - [[Retinol#Night vision|Night blindness]]. Persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes. Some other ocular changes are referred to as [[xerophthalmia]]. First there is dryness of the conjunctiva ([[xerosis]]) as the normal lacrimal and mucus secreting epithelium is replaced by a keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques ([[Bitot's spots]]) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea ([[keratomalacia]]) and total blindness.<ref name="pmid16513513">{{cite journal |author=Roncone DP |title=Xerophthalmia secondary to alcohol-induced malnutrition |journal=Optometry (St. Louis, Mo.) |volume=77 |issue=3 |pages=124–33 |year=2006 |pmid=16513513 |doi=10.1016/j.optm.2006.01.005 |accessdate=2007-08-18}}</ref> Other changes include impaired immunity, hypokeratosis (white lumps at hair follicles), [[keratosis pilaris]] and [[squamous metaplasia]] of the epithelium lining the upper respiratory passages and urinary bladder to a keratinized epithelium. With relations to dentistry, a deficiency in Vitamin A leads to enamel hypoplasia.
Adequate supply of Vitamin A is especially important for pregnant and breastfeeding women, since deficiencies cannot be compensated by [[postnatal]] supplementation.<ref>{{cite journal |author=Strobel M, Tinz J, Biesalski HK |title=The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women |journal=Eur J Nutr |volume=46 Suppl 1 |issue= |pages=I1–20 |year=2007 |pmid=17665093 |doi=10.1007/s00394-007-1001-z}}</ref><ref>{{cite journal |author=Schulz C, Engel U, Kreienberg R, Biesalski HK |title=Vitamin A and beta-carotene supply of women with gemini or short birth intervals: a pilot study |journal=Eur J Nutr |volume=46 |issue=1 |pages=12–20 |year=2007 |pmid=17103079 |doi=10.1007/s00394-006-0624-9}}</ref>.
==Toxicity==
{{Main|Hypervitaminosis A}}
As vitamin A is fat-soluble, disposing of any excesses taken in through diet is much harder than with water-soluble vitamins B and C. As such, vitamin A toxicity can result. This can lead to nausea, jaundice, irritability, [[Anorexia (symptom)|anorexia]] (not to be confused with [[anorexia nervosa]], the eating disorder), vomiting, blurry vision, headaches, muscle and abdominal pain and weakness, drowsiness and altered mental status.
Acute toxicity generally occurs at doses of 25,000 [[International unit|IU]]/[[Kilogram|kg]], with chronic toxicity occurring at 4,000 IU/kg daily for 6-15 months.<ref>{{cite web |url=http://www.emedicine.com/emerg/topic638.htm |title=Toxicity, Vitamin |accessmonthday= |accessyear= |last=Rosenbloom |first=Mark |date= |work=eMedicine |publisher= }}</ref> However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day. In people with renal failure 4000 IU can cause substantial damage. Additionally excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1500IU/kg of body weight.<ref name="Penniston2006" />
In chronic cases, hair loss, drying of the mucous membranes, fever, [[insomnia]], fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity.<ref>{{cite web |url=http://www.emedicine.com/med/topic2382.htm |title=Vitamin A Toxicity |accessmonthday= |accessyear= |last=Eledrisi |first=Mohsen S. |date= |work=eMedicine |publisher= }}</ref>
It has been estimated that 75% of people may be ingesting more than the RDA for vitamin A on a regular basis in developed nations. Intake of twice the RDA of preformed vitamin A chronically may be associated with osteoporosis and hip fractures. High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high vitamin A intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyoid hormone which regulates calcium.<ref name="Penniston2006">{{ cite journal | last = Penniston | first = Kristina L. | authorlink = | coauthors = Tanumihardjo, Sherry A. | year = 2006 | month = | title = The acute and chronic toxic effects of vitamin A | journal = [[American Journal of Clinical Nutrition|Am. J. Clin. Nutr.]] | volume = 83 | issue = 2 | pages = 191–201 | pmid = 16469975 | url = http://www.ajcn.org/cgi/content/abstract/83/2/191 | accessdate = | quote = }}</ref>
Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis.<ref name="Combs2008">{{cite book |title=The Vitamins: Fundamental Aspects in Nutrition and Health |last=Combs |first=Gerald F. |authorlink= |coauthors= |year=2008 |edition=3rd edition |publisher=Elsevier Academic Press |location=Burlington |isbn=9780121834937 |pages= }}</ref>
These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, but excessive dietary intake of beta-carotene can lead to [[carotenodermia]], which causes orange-yellow discoloration of the skin.<ref name="pmid15575851">{{cite journal |author=Sale TA, Stratman E |title=Carotenemia associated with green bean ingestion |journal=Pediatr Dermatol |volume=21 |issue=6 |pages=657–9 |year=2004 |pmid=15575851 |doi=10.1111/j.0736-8046.2004.21609.x}}</ref><ref name="pmid9830271">{{cite journal |author=Nishimura Y, Ishii N, Sugita Y, Nakajima H |title=A case of carotenodermia caused by a diet of the dried seaweed called Nori |journal=J. Dermatol. |volume=25 |issue=10 |pages=685–7 |year=1998 |pmid=9830271 |doi=}}</ref><ref name="pmid16556283">{{cite journal |author=Takita Y, Ichimiya M, Hamamoto Y, Muto M |title=A case of carotenemia associated with ingestion of nutrient supplements |journal=J. Dermatol. |volume=33 |issue=2 |pages=132–4 |year=2006 |pmid=16556283 |doi=10.1111/j.1346-8138.2006.00028.x}}</ref>
A study by Siri Forsmo ''et al.'' shows a correlation between low bone mineral density and too high intake of vitamin A.<ref name="Forsmo2008">{{ cite journal | last = Forsmo | first = Siri | authorlink = | coauthors = Fjeldbo,Sigurd Kjørstad; Langhammer, Arnulf | year = 2008 | month = | title = Childhood Cod Liver Oil Consumption and Bone Mineral Density in a Population-based Cohort of Peri- and Postmenopausal Women: The Nord-Trøndelag Health Study | journal = [[American Journal of Epidemiology|Am. J. Epidemiol.]] | volume = 167 | issue = 4 | pages = 406–411 | doi = 10.1093/aje/kwm320 | url = | accessdate = | quote = | pmid=18033763 }}</ref>
Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity.<ref>Science News. [http://findarticles.com/p/articles/mi_m1200/is_n13_v135/ai_7502207 Water-soluble vitamin A shows promise.]</ref> However, a 2003 study found that water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin.<ref name="pmid14668278">{{cite journal |author=Myhre AM, Carlsen MH, Bøhn SK, Wold HL, Laake P, Blomhoff R |title=Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations |journal=Am. J. Clin. Nutr. |volume=78 |issue=6 |pages=1152–9 |year=2003 |month=December |pmid=14668278 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=14668278}}</ref>
A 2006 study found that children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins.<ref name="pmid17157660">{{cite journal |author=Kull I, Bergström A, Melén E, ''et al'' |title=Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood |journal=J. Allergy Clin. Immunol. |volume=118 |issue=6 |pages=1299–304 |year=2006 |month=December |pmid=17157660 |doi=10.1016/j.jaci.2006.08.022 |url=http://www.jacionline.org/article/S0091-6749(06)01775-1/abstract}}</ref>
==See also==
* [[Beta carotene]]
* [[Retinoids]]
* [[Hypervitaminosis A]]
==References==
{{Reflist|2}}
==Further reading==
*{{cite book |title=Vitamin A |series=Vitamins and Hormones |volume=75 |last=Litwack |first=Gerald |authorlink= |coauthors= |year=2007 |publisher=Elsevier Academic Press |location=San Diego, CA |isbn=9780127098753 |pages= }}
==External links==
* {{MeshName|Vitamin+A}}
* [http://www.vitaminA.org vitaminA.org]
{{Vitamin}}
[[Category:Vitamins|A]]
{{Link FA|hr}}
[[ar:فيتامين ألف]]
[[bs:Vitamin A]]
[[ca:Retinol]]
[[cs:Vitamín A]]
[[de:Retinol]]
[[dv:ވިޓަމިން އޭ]]
[[et:A-vitamiin]]
[[es:Vitamina A]]
[[eo:Vitamino A]]
[[eu:A bitamina]]
[[fa:ویتامین آ]]
[[fr:Vitamine A]]
[[gl:Vitamina A]]
[[ko:비타민 A]]
[[hr:Vitamin A]]
[[id:Retinol]]
[[is:A-vítamín]]
[[it:Retinolo]]
[[he:ויטמין A]]
[[ku:Rêtînol]]
[[lv:A vitamīns]]
[[lb:Retinol]]
[[lt:Vitaminas A]]
[[jbo:abumoi mivytcuxu'i]]
[[ml:ജീവകം എ]]
[[mr:अ-जीवनसत्त्व]]
[[ms:Vitamin A]]
[[nl:Retinol]]
[[ja:ビタミンA]]
[[no:Vitamin A]]
[[oc:Vitamina A]]
[[pl:Witamina A]]
[[pt:Vitamina A]]
[[ro:Retinol]]
[[ru:Ретинол]]
[[sq:Vitamina A]]
[[simple:Vitamin A]]
[[sk:Retinol]]
[[sl:Vitamin A]]
[[sr:Ретинол]]
[[sh:Vitamin A]]
[[fi:A-vitamiini]]
[[sv:Retinol]]
[[te:విటమిన్ ఎ]]
[[vi:Vitamin A]]
[[tr:A vitamini]]
[[uk:Вітамін A]]
[[zh:維生素A]]