Vitamin A is a fat-soluble vitamin essential for various functions: vision, immune function, reproduction, and cellular communication.
It has multiple forms: retinol, retinal, and retinoic acid, which are derived from dietary sources.
Animal-based foods provide preformed vitamin A, while plant-based foods contain provitamin A carotenoids, such as beta-carotene, which are converted into active forms in the body.
Vitamin A plays a crucial role in vision by forming the chromophore 11-cis retinal, which is essential for phototransduction in the retina.
Vitamin A also regulates gene expression through retinoic acid, which binds to nuclear receptors like retinoic acid receptors and retinoid X receptors influencing cell differentiation, growth, and immune function.
Deficiency in vitamin A can lead to severe health issues, including blindness, immune dysfunction, and increased susceptibility to infections.
Excessive intake can cause toxicity: liver damage and other adverse effects.
Vitamin A is crucial for maintaining epithelial integrity, supporting immune responses, and modulating T cell function.
Overall, vitamin A is indispensable for maintaining health and preventing disease, with its roles extending from vision to immune regulation and cellular differentiation.
Retinol and retinal play a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription.
Retinol: Routes of administration by mouth, intramuscular.
Vitamin A encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most notably β-carotene (beta-carotene).
Vitamin A has multiple functions: growth during embryo development, maintaining the immune system, and healthy vision.
For aiding vision it combines with the protein opsin to form rhodopsin, the light-absorbing molecule necessary for both low-light and color vision.
Vitamin A occurs as two principal forms in foods: A) retinoids, found in animal-sourced foods, either as retinol or bound to a fatty acid to become a retinyl ester.
B) the carotenoids α-carotene, β-carotene, γ-carotene and the xanthophyll beta-cryptoxanthin that function as provitamin A in herbivore and omnivore animals which possess the enzymes that cleave and convert provitamin carotenoids to retinol.
Dietary retinol is absorbed from the digestive tract via passive diffusion.
Unlike retinol, β-carotene is taken up by enterocytes by the membrane transporter protein scavenger receptor B1 (SCARB1).
Retinol is stored in lipid droplets in the liver.
A well-nourished humans can go months on a vitamin A-deficient diet, while maintaining blood levels in the normal range.
Only when the liver stores are nearly depleted will signs and symptoms of deficiency show.
Retinol is reversibly converted to retinal, then irreversibly to retinoic acid, which activates hundreds of genes.
Vitamin A deficiency is common in developing countries, especially in Sub-Saharan Africa and Southeast Asia.
Deficiency can occur at any age but is most common in pre-school age children and pregnant women, the latter due to a need to transfer retinol to the fetus.
Vitamin A deficiency is estimated to affect approximately one-third of children under the age of five around the world, resulting in hundreds of thousands of cases of blindness and deaths from childhood diseases because of immune system failure.
Reversible night blindness is an early indicator of low vitamin A status.
Plasma retinol is used as a biomarker to confirm vitamin A deficiency.
Breast milk retinol can indicate a deficiency in nursing mothers.
Neither breast milk or plasma retinol measures indicates the status of liver reserves.
Vitamin A toxicity also referred to as hypervitaminosis A, occurs when there is too much vitamin A accumulating in the body.
Vitamin A toxicity 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 of high dose supplements is stopped.
Vitamin A is a fat-soluble vitamin, a category that also includes vitamins D, E and K.
Vitamin A encompasses several chemically related naturally occurring compounds or metabolites, (vitamers), that all contain a β-ionone ring.
The primary dietary form is retinol, which may have a fatty acid molecule attached, creating a retinyl ester, when stored in the liver.
Retinol – the transport and storage form of vitamin A – is interconvertible with retinal, catalyzed to retinal by retinol dehydrogenases and back to retinol by retinaldehyde reductases.
Retinal,also known as retinaldehyde, can be irreversibly converted to all-trans-retinoic acid by the action of retinal dehydrogenase
retinal + NAD+ + H2O → retinoic acid + NADH + H+
Retinoic acid is actively transported into the cell nucleus where it regulates thousands of genes by binding directly to gene targets via retinoic acid receptors.
In addition to retinol, retinal and retinoic acid, plant-, fungi- or bacteria-sourced carotenoids can be metabolized to retinol, and are thus vitamin A vitamers.
There are also what are referred to as 2nd, 3rd and 4th generation retinoids which are not considered vitamin A vitamers because they cannot be converted to retinol, retinal or all-trans-retinoic acid.
Retinyl esters from animal-sourced foods or synthesized for dietary supplements are acted upon by retinyl ester hydrolases in the lumen of the small intestine to release free retinol.
Retinol enters enterocytes by passive diffusion.
Absorption efficiency is in the range of 70 to 90%.
There is a risk for acute or chronic vitamin A toxicity because there are no mechanisms to suppress absorption or excrete the excess in urine.
Within the cell, retinol is bound to retinol binding protein 2 (RBP2), and then enzymatically re-esterified by the action of lecithin retinol acyltransferase and incorporated into chylomicrons that are secreted into the lymphatic system.
Unlike retinol, β-carotene is taken up by enterocytes by the membrane transporter protein scavenger receptor B1 (SCARB1).
SCARB1 protein is upregulated in times of vitamin A deficiency, and vitamin A status is in the normal range, SCARB1 is downregulated, reducing absorption.
Absorbed β-carotene is either incorporated as such into chylomicrons or first converted to retinal and then retinol, bound to RBP2.
After a meal, roughly two-thirds of the chylomicrons are taken up by the liver with the remainder delivered to peripheral tissues.
Peripheral tissues also can convert chylomicron β-carotene to retinol.
The capacity to store retinol in the liver means that the well-nourished 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, then bind retinol to retinol-binding protein 4 (RBP4), and transfer the retinol-RBP4 to HSCs for storage in lipid droplets as retinyl esters.
After a meal or when consumption of large amounts exceeds liver storage capacity, more than 95% of retinol in circulation is bound to RBP4.
The liver content of vitamin A can range from 20 to 30 μg/gram wet weight.
Polar bear liver is acutely toxic to humans because content has been reported in range of 2,215 to 10,400 μg/g wet weight.
Retinol circulates bound to RBP4.
In the liver and peripheral tissues retinol is reversibly converted to retinal by the action of alcohol dehydrogenases, which are also responsible for the conversion of ethanol to acetaldehyde.
Retinal is irreversibly oxidized to retinoic acid (RA) by the action of aldehyde dehydrogenases.
RA regulates the activation or deactivation of genes.
The oxidative degradation of RA is induced by RA, i.e, its presence triggers its removal, making for a short-acting gene transcription signal.
This deactivation is mediated by a cytochrome P450 (CYP) enzyme system, specifically enzymes CYP26A1, CYP26B1 and CYP26C1.
CYP26A1 is the predominant form in the human liver; all other human adult tissues contained higher levels of CYP26B1.
Other than for vision, the metabolic functions of vitamin A are mediated by all-trans-retinoic acid (RA).
The formation of RA from retinal is irreversible.
To prevent accumulation of RA it is oxidized and eliminated fairly quickly.
Three cytochromes catalyze the oxidation of retinoic acid, and the genes for Cyp26A1, Cyp26B1 and Cyp26C1 are induced by high levels of RA, providing a self-regulating feedback loop.
Vitamin A status involves eye health via two separate functions: essential factor in rod cells and cone cells in the retina responding to light exposure by sending nerve signals to the brain, and vitamin A in the form of retinoic acid is essential to normal epithelial cell functions.
An early sign of vitamin A deficiency is night blindness.
Vitamin A in the form of retinoic acid is essential to normal epithelial cell functions.
Severe vitamin A deficiency, common in infants and young children in southeast Asia causes xerophthalmia characterized by dryness of the conjunctival epithelium and cornea.
Untreated, xerophthalmia progresses to corneal ulceration and blindness.
The role of vitamin A in the visual cycle is related to the retinal compound: Retinol is converted by the enzyme RPE65 within the retinal pigment epithelium into 11-cis-retinal.
11-cis-retinal is bound to the protein opsin to form rhodopsin in rod cells and iodopsin in cone cells.
As light enters the eye, the 11-cis-retinal is isomerized to the all-trans form which dissociates from the opsin in a series of steps called photo-bleaching.
Isomerization induces a nervous signal along the optic nerve to the visual center of the brain.
After separating from opsin, the all-trans-retinal is recycled and converted back to the 11-cis-retinal form by a series of enzymatic reactions.
It then completes the cycle by binding to opsin to reform rhodopsin in the retina.
A deficiency in vitamin A will inhibit the reformation of rhodopsin, and will lead to one of the first symptoms, night blindness.
Vitamin A deficiency-caused night blindness is a reversible difficulty for the eyes to adjust to dim light.
It is common in young children who have a diet inadequate in retinol and β-carotene.
Dark adaptation typically causes an increase in photopigment amounts in response to low levels of illumination.
This increases light sensitivity by up to 100,000 times compared to normal daylight conditions.
Significant improvement in night vision takes place within ten minutes, but the process can take up to two hours to reach maximal effect.
Xerophthalmia, caused by a severe vitamin A deficiency, is characterized by pathologic dryness of the conjunctival epithelium and cornea.
Xerophthalmia-The conjunctiva becomes dry, thick, and wrinkled, and is Indicative in the appearance of Bitot’s spots, which are clumps of keratin debris that build up inside the conjunctiva.
If untreated, xerophthalmia can lead to dry eye syndrome, corneal ulceration and ultimately to blindness as a result of cornea and retina damage.
Throughout southeast Asia, it is estimated that more than half of children under the age of six years have subclinical vitamin A deficiency and night blindness.
The progression to xerophthalmia is the leading cause of preventable childhood blindness.
Estimates are that each year there are 350,000 cases of childhood blindness due to vitamin A deficiency.
The causes are vitamin A deficiency during pregnancy, followed by low transfer of vitamin A during lactation and infant/child diets low in vitamin A or β-carotene.
Childhood vitamin A deficiency significantly increases all-cause mortality.
Vitamin A deficiency, using serum retinol less than 0.70 μmol/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).
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 vitamin A deficiency.
Retinoic acid regulates gene transcription by binding to nuclear receptors known as retinoic acid receptors (RARs; RARα, RARβ, RARγ) which are bound to DNA as heterodimers which must dimerize before they can bind to the DNA.
Expression of more than 500 genes is responsive to retinoic acid.
RA has a pivotal role during development, and altered levels of endogenous RA signaling during early embryology, either too low or too high, leads to birth defects, including congenital vascular and cardiovascular defects.
In the fetal alcohol spectrum disorder which encompasses congenital anomalies, including craniofacial, auditory, and ocular defects, neurobehavioral anomalies and mental disabilities caused by maternal consumption of alcohol during pregnancy.
It is proposed that in the embryo there is competition between acetaldehyde, an ethanol metabolite, and retinal for aldehyde dehydrogenase activity, resulting in a retinoic acid deficiency, and attributing the congenital birth defects to the loss of RA activated gene activation.
The prescription drugs tretinoin (all-trans-retinoic acid) and isotretinoin (13-cis-retinoic acid), used orally or topically for acne treatment, are labeled with boxed warnings for pregnant women or women who may become pregnant, as they are known human teratogens.
Vitamin A deficiency has been linked to compromised resistance to infectious diseases.
In countries where early childhood vitamin A deficiency is common, vitamin A supplementation reduces the incidence of diarrhea and measles, and all-cause mortality.
Vitamin A deficiency also increases the risk of immune system over-reaction, leading to chronic inflammation in the intestinal system, stronger allergic reactions and autoimmune diseases.
Retinoic acid (RA) triggers receptors in bone marrow, resulting in generation of new white blood cells.
RA regulates proliferation and differentiation of white blood cells, the directed movement of T cells to the intestinal system, and to the up- and down-regulation of lymphocyte function.
If RA is adequate, T helper cell subtype Th1 is suppressed and subtypes Th2, Th17 and iTreg (for regulatory) are induced.
Dendritic cells located in intestinal tissue have enzymes that convert retinal to all-trans-retinoic acid, to be taken up by retinoic acid receptors on lymphocytes.
The process triggers gene expression that leads to T cell types Th2, Th17 and iTreg moving to and taking up residence in mesenteric lymph nodes and Peyer’s patches, respectively outside and on the inner wall of the small intestine.
The net effect is a down-regulation of immune activity, seen as tolerance of food allergens, and tolerance of resident bacteria and other organisms in the microbiome of the large intestine.
In a vitamin A deficient state, innate immunity is compromised and pro-inflammatory Th1 cells predominate.
Retinoic acid is essential for balanced T helper cell responses. It promotes the differentiation of regulatory T cells (Tregs) while suppressing pro-inflammatory Th17 cell development.
This helps maintain immune tolerance and prevents excessive inflammatory responses.
RA supports antibody class switching, particularly to IgA, which is crucial for mucosal immunity, and enhances B cell activation and proliferation in response to antigens.
Dendritic cells in gut-associated lymphoid tissues convert vitamin A to retinoic acid, which then promotes the expression of gut-homing receptors on T and B cells, directing them to mucosal sites.
RA helps maintain the integrity of mucosal barriers by supporting epithelial cell differentiation and tight junction formation, which is the first line of defense against pathogens.
Retinoic acid enhances macrophage antimicrobial activity and supports their ability to clear infections.
Retinoic acid promotes the resolution of inflammation by supporting macrophage polarization toward anti-inflammatory phenotypes.
RA influences dendritic cell development and their ability to present antigens effectively to T cells.
Vitamin A deficiency leads to increased susceptibility to infections, particularly respiratory and gastrointestinal infections, highlighting retinoic acid’s critical role in immune competence.
The effects of retinoic acid depend on the local concentration, timing, and the specific immune cell types involved, making it a sophisticated regulator of immune responses.
Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death.
A meta-analysis of clinical trials conducted in countries where VAD is prevalent concluded that when children were supplemented with vitamin A, there was a 50% reduction in incidence of contracting measles.
Vitamin A supplementation is not thought to reduce the risk of death from measles.
Young children, however, given high doses of vitamin A from supplements or cod liver oil can accumulate to toxic levels and this can lead to hypervitaminosis A and liver damage.
In the 2025 Southwest United States measles outbreak, centered in West Texas some families continued to refuse vaccines and instead opted for giving vitamin A supplements or vitamins A- and D-containing cod liver oil.
Multiple children hospitalized for measles at Covenant Children’s Hospital in Lubbock also showed signs of liver damage, a symptom of vitamin A toxicity.
Deficiencies in vitamin A have been linked to an increased susceptibility to skin infection and inflammation.Vitamin A modulates the innate immune response and maintains homeostasis of epithelial tissues and mucosa through its metabolite, retinoic acid (RA).
As part of the innate immune system, toll-like receptors in skin cells respond to pathogens and cell damage by inducing a pro-inflammatory immune response which includes increased RA production.
Keratinocytes of the epidermal layer of the skin produce and secrete antimicrobial peptides (AMPs), resistin and cathelicidin, and are promoted by RA.
Dietary recommendations (μg/day) Infants 0–6 months 400 adequate intake(AI) -600 upper limits 7–12 months 500 (AI) 600 Children 1–3 years 300 600 4–8 years 400 900 Males 9–13 years 600 1700 14–18 years 900 2800 >19 years 900 3000 Females 9–13 years 600 1700 14–18 years 700 2800 >19 years 700 3000 Pregnancy <19 years 750 2800 >19 years 770 3000 Lactation <19 years 1200 2800 >19 years 1300 3000
Vitamin A toxicity (hypervitaminosis A) occurs when too much vitamin A accumulates in the body.
It comes from consumption of preformed vitamin A but not of carotenoids, as conversion of the latter to retinol is suppressed by the presence of adequate retinol.
Retinol safety:Hypervitaminosis A
There are historical reports of acute hypervitaminosis from explorers consuming bearded seal or polar bear liver, both very rich sources of stored retinol, and there are also case reports of acute hypervitaminosis from consuming fish liver.
Generally 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.
Acute toxicity occurs after a single or short-term doses of greater than 150,000 μg.
Symptoms of vitamin A toxicity 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.
Chronic toxicity may occur with long-term consumption of vitamin A at doses of 25,000–33,000 IU/day for several months.
Excessive consumption of alcohol can lead to chronic toxicity at lower intakes.
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.
During pregnancy, especially during the first trimester, consumption of retinol in amounts exceeding 4,500 μg/day increased the risk of birth defects.
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.
No adverse effects other than carotenemia have been reported for consumption of β-carotene rich foods.
Supplementation with β-carotene does not cause hypervitaminosis A.
High-dose β-carotene or retinol supplementation resulted in a higher incidence of lung cancer and of total mortality due to cardiac mortality.
Carotenoderma, also referred to as carotenemia, is a benign and reversible medical condition where an excess of dietary carotenoids results in orange discoloration of the outermost skin layer.
It is associated with a high blood β-carotene value.
Carotenoderma can occur after a month or two of consumption of β-carotene rich foods, such as carrots, carrot juice, tangerine juice, mangos, or in Africa, red palm oil. β-carotene dietary supplements can have the same effect.
The discoloration extends to palms and soles of feet, but not to the white of the eye, which helps distinguish the condition from jaundice.
Consumption of greater than 30 mg/day for a prolonged period has been confirmed as leading to carotenemia.
For vitamin A labeling purposes, 100% of the Daily Value was set at 5,000 IU, but it was revised to 900 μg RAE(retinol active equivalents).
cod liver oil 30,000 beef liver (cooked) 4,970–21,145 chicken liver (cooked) 4,296 butter (stick) 684 cheddar cheese 316 egg (cooked) 140
Vitamin A is found in many foods.
Vitamin A in food exists either as preformed retinol – an active form of vitamin A – found in animal liver, dairy and egg products, and some fortified foods, or as provitamin A carotenoids, which are plant pigments digested into vitamin A after consuming carotenoid-rich plant foods, typically in red, orange, or yellow colors.
Carotenoid pigments may be masked by chlorophylls in dark green leaf vegetables, such as spinach.
The relatively low bioavailability of plant-food carotenoids results partly from binding to proteins – chopping, homogenizing or cooking disrupts the plant proteins, increasing provitamin A carotenoid bioavailability.
Vegetarian and vegan diets can provide sufficient vitamin A in the form of provitamin A carotenoids if the diet contains carrots, carrot juice, sweet potatoes, green leafy vegetables such as spinach and kale, and other carotenoid-rich foods.
In the U.S., the average daily intake of β-carotene is in the range 2–7 mg.
Some countries require or recommend fortification of foods.
μg RAE per 100 g
Sweet potato, baked, no added fat 957
Carrot, frozen, cooked, no added fat 843
Pumpkin, canned, cooked 767
Spinach, fresh, cooked, no added fat 341
Kale, fresh, cooked, no added fat 245
Delivery of oral high-dose supplements remains the principal strategy for minimizing deficiency.
Vitamin A deficiency is common in developing countries, especially in Sub-Saharan Africa and Southeast Asia.
Deficiency can occur at any age, but is most common in pre-school-age children and pregnant women, the latter due to a need to transfer retinol to the fetus.
The causes are low intake of retinol-containing, animal-sourced foods and low intake of carotene-containing, plant-sourced foods.
Vitamin A deficiency is estimated to affect approximately one third of children under the age of five around the world, possibly leading to the deaths of 670,000 children under five annually.
Between 250,000 and 500,000 children in developing countries become blind each year owing to vitamin A deficiency.
Vitamin A deficiency is the leading cause of preventable childhood blindness.
Vitamin A deficiency also increases the risk of death from common childhood conditions, such as diarrhea.
Night blindness and dry eyes are signs of vitamin A deficiency and can be recognized without requiring biochemical tests.
Plasma retinol is used to confirm vitamin A status.
A plasma concentration of about 2.0 μmol/L is normal; less than 0.70 μmol/L (equivalent to 20 μg/dL) indicates moderate vitamin A deficiency, and less than 0.35 μmol/L (10 μg/dL) indicates severe vitamin A deficiency.
Breast milk retinol of less than 8 μg/gram milk fat is considered insufficient.
The amount of vitamin A leaving the liver, bound to retinol binding protein (RBP), is under tight control as long as there are sufficient liver reserves.
Only when liver content of vitamin A drops below approximately 20 μg/gram will concentration in the blood decline.
Secondary 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.
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.
Vitamin A appears to be involved in the pathogenesis of anemia by diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection , and mobilization of iron stores from tissues.
All vertebrate and chordate species require vitamin A, either as dietary carotenoids or preformed retinol from consuming other animals.
Before the era of synthetic retinol, cod liver oil, high in vitamins A and D, was a commonly consumed dietary supplement.
Governments and non-government organizations promoting vitamin A fortification of foods and creating programs that administer large bolus-size oral doses of vitamin A to young children every four to six months.
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%.
There is 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.
Acne-Topical retinoic acid and retinol
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.
Retinoic acids tretinoin (all-trans-retinoic acid) and isotretinoin (13-cis-retinoic acid) are prescription topical medications used to treat moderate to severe cystic acne and acne not responsive to other treatments.
These are usually applied as a 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).
This process contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation.
The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation.
Retinoic acid products also reduce sebum secretion, a nutrient source for bacteria, from facial pores.
These drugs should not be used by pregnant women or women who are anticipating becoming pregnant.
Non-prescription 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: 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.
Some evidence with human skin that esterified retinol is absorbed and then converted to retinol.
Oral isotretinoin is recommended for treating treatment resistant acne, acne that can lead to scarring, and acne that is associated with psychosocial distress.
It is approved by the FDA for treating severe acne vulgaris that is resistant to other treatments.
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.
Neurocognitive impairments in the absence of any physical defects has been established to be 30–60%.
It is recommended 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.
Isotretinoin treatment for severe and refractory acne vulgaris at a dose of 0.5–1.0 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.
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 into mature epidermal cells.
RA reduces the size and secretion of the sebaceous glands, and by doing so reduces bacterial numbers in both the ducts and skin surface.
It reduces inflammation via inhibition of chemotactic responses of monocytes and neutrophils.
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 interferon-alpha showed some potential for treating genital warts, treating precancerous skin lesions and skin cancer.
Isotretinoin in combination with topical fluorouracil showed some potential for treating precancerous skin lesions and skin cancer.
Vitamin A plays an important role in the body’s immune function, both the adaptive response, and to help the body fight off infection.
The anti-inflammatory effects of vitamin A also contribute to repairing mucosal cells that can be damaged by 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 does not support vitamin A as being effective or having a benefit.
Supplementation with β-carotene did not appear to decrease the risk of cancer overall, nor specific cancers including: pancreatic, colorectal, prostate, breast, melanoma, or skin cancer generally.
High-dose β-carotene supplementation unexpectedly resulted in a higher incidence of lung cancer and of total mortality in people who were cigarette smokers.
For dietary retinol, no effects were observed for high dietary intake and breast cancer survival, risk of liver cancer, risk of bladder cancer or risk of colorectal cancer, although the last review did report lower risk for higher β-carotene consumption.
An inverse association was reported between retinol intake and relative risk of esophageal cancer, gastric cancer, ovarian cancer, pancreatic cancer, lung cancer, melanoma, and cervical cancer.
For lung cancer, an inverse association was also seen for β-carotene intake, separate from the retinol results.
When high dietary intake was compared to low dietary intake, the decreases in relative risk were in the range of 15 to 20%.
For gastric cancer, a meta-analysis of prevention trials reported a 29% decrease in relative risk from retinol supplementation at 1500 μg/day.
Fetal alcohol spectrum disorder (FASD), formerly referred to as fetal alcohol syndrome, presents as craniofacial malformations, neurobehavioral disorders and mental disabilities, all attributed to exposing human embryos to alcohol during fetal development.
The risk of FASD depends on the amount consumed, the frequency of consumption, and the points in pregnancy at which the alcohol is consumed.
Ethanol is a known teratogen, and is metabolized by alcohol dehydrogenase enzymes into acetaldehyde,
The subsequent oxidation of acetaldehyde into acetate is performed by aldehyde dehydrogenase enzymes.
Retinoic acid (RA) regulates numerous embryonic and differentiation processes, one of the proposed mechanisms for the teratogenic effects of ethanol is a competition for the enzymes required for the biosynthesis of RA from vitamin A.
Malaria and vitamin A deficiency are both common among young children in sub-Saharan Africa.
Vitamin A supplementation to children in regions where vitamin A deficiency is common has repeatedly been shown to reduce overall mortality rates, especially from measles and diarrhea.
For malaria, clinical trial results are mixed, either showing that vitamin A treatment did not reduce the incidence of probable malarial fever, or else did not affect incidence, but did reduce slide-confirmed parasite density and reduced the number of fever episodes.
Vitamin A administration is recommended for all children with severe measles, such as those requiring hospitalization, to reduce the risk of complications.
Vitamin A supplementation has been shown to decrease mortality and the risk of complications in young children hospitalized with measles, and is effective in reducing the severity of measles infection and associated complications such as pneumonia and diarrhea.
Measles can deplete vitamin A stores and worsen outcomes.
In high-income countries like the U.S., where vitamin A deficiency is rare, the benefit is less clear, but it is still recommended for severe cases.
Vitamin A does not prevent or cure measles, and vaccination remains the best prevention.