Natural Standard® Patient Monograph, Copyright © 2014 (www.naturalstandard.com). All Rights Reserved. Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions. Background Vitamin A is a fat-soluble vitamin that comes from two sources: preformed retinoids and provitamin carotenoids. Retinoids, such as retinal and retinoic acid, are found in animal sources such as liver, kidney, eggs, and dairy products. Carotenoids, such as beta-carotene (which has the highest vitamin A activity), are found in plants such as dark or yellow vegetables and carrots. Natural retinoids are present in all living organisms, either as preformed vitamin A or as carotenoids, and are required for biological processes such as vision and cellular growth. A major biologic function of vitamin A (as the metabolite retinal) is in the visual cycle. Research also suggests that vitamin A may reduce death from measles, prevent some types of cancer, aid in growth and development, and improve immune function. Recommended dietary allowance (RDA) levels for vitamin A oral intake have been established by the U.S. Institute for Medicine of the National Academy of Sciences to prevent deficiencies in vitamin A. At recommended doses, vitamin A is considered nontoxic. Excess dosing may lead to short or long-term toxicity. Vitamin A deficiency is rare in developed nations but remains a concern in developing countries, particularly in areas where poor nutrition is common. Prolonged deficiency can lead to xerophthalmia (dry eye) and ultimately to night blindness or total blindness, as well as to skin disorders, infections (such as measles), diarrhea, and lung disorders. Related terms 3,7-Dimethyl-9-(2,6,6,trimethyl-1-cyclohexen-1-yl)-2,4,6,8-natetraen-1-ol, 3-dehydroretinol, Accutane®, acitretin, adapalene, alitretinoin, all-trans retinoic acid, Altinac®, Amnesteem®, antixerophthalmic vitamin, Aquasol A®, Avita®, axerophtholum, beta-carotene, beta-carotene oleovitamin A, bexarotene, carotenoids, Differin®, etretinate, isotretinoin, Palmitate-A®, Renova®, Retin-A®, Retin-A Micro®, retinaldehyde (RAL), retinyl acetate, retinyl N-formyl aspartamate, retinyl palmitate, retinoic acid, retinol, Solatene®, Soriatane®, SourceCF®, Targretin®, tazarotene, Tazorac®, Tegison®, topical retinoids, tretinoin, Vesabiod®, Vesanoid®, Vitamax®, vitamin A USP, vitamin A1, vitamina A, vitaminum A. Dosing The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy. Adults (18 years and older) Vitamin A is found in dairy products, fish, and darkly colored fruits and vegetables. Five servings of fruits and vegetables daily supplies 5-6 milligrams of provitamin A carotenoids, which provides about 50-65% of the adult recommended dietary allowance (RDA) for vitamin A. Vitamin A is included in most multivitamins, and the U.S. recommended dietary allowance (RDA) for adults is as follows: 900 micrograms daily (3,000 IU) for men and 700 micrograms daily (2,300 IU) for women; for pregnant women 19 years old and older, 770 micrograms daily (2,600 IU); and for lactating women 19 years old and older, 1,300 micrograms daily (4,300 IU). For vitamin A deficiency, unrelated to xerophthalmia (dry eye), vitamin A has been given at a daily dose of 100,000 IU by mouth or intramuscularly for three days, followed by 50,000 IU daily for two weeks. After two weeks, daily doses of 10,000-20,000 IU have been given for two months. In mothers six weeks after childbirth, either 400,000 IU of vitamin A (in two doses separated by 24 hours) or 200,000 IU as one dose (plus placebo 24 hours later) has been taken. For community based intervention, a single dose of 200,000 IU has been given by mouth as monthly doses for six months, four months, or one month. For acne, isotretinoin was given by mouth daily as 0.5-0.7 milligrams per kilogram (normal and intermittent dose) or 0.25-0.4 milligrams per kilogram daily (low-dose) for one out of every four weeks. Vitamin A and retinoids are available as gels, creams, and liquids and are typically applied to the skin once daily but can be used every other day if poorly tolerated. Tretinoin 0.025% and adapalene 0.1% have been applied to the skin once to twice daily for up to 16 weeks. For acute promyelocytic leukemia (treatment), all-trans retinoic acid (Vesanoid® (tretinoin)) has been administered as follows: 45 milligrams per square meter of body surface area daily by mouth, as two evenly divided doses until complete remission; therapy should be discontinued 30 days after the achievement of complete remission or after 90 days of treatment, whichever occurs first. In addition, 25-45 milligrams per square meter daily or 30-40 milligrams of all trans-retinoic acid (ATRA) has been taken daily for two to three years. For arthritis, 0.5 milligrams per kilogram of etretinate (vitamin A form) was taken daily for four weeks then reduced to 0.25 milligrams per kilogram daily if there was a lack of improvement or if side effects were observed. Vitamin A was also given as 50,000 IU daily for three weeks; however, further research concluded that there was a lack of convincing evidence that vitamin A is effective for treating any type of arthritis. For breast cancer, 1,000-6,000 milligrams of retinol and 3,000 IU-10,000 IU of vitamin A has been taken daily. For cancer of the stomach and intestine, 5,000 IU and 50,000 IU have been administered in weekly doses; however, research suggests that these doses of vitamin A may have been associated with an increased risk of mortality. For cancer (general), 20-50 milligrams of beta-carotene was given by mouth daily or every other day for 5-12 years. For cancer-related side effects, weekly injections of 100,000 IU of vitamin A have been used. For cervical cancer, vitamin A supplementation (dosing information was lacking) was taken for 1-3 years. For colorectal cancer, 25,000 IU of vitamin A in combination with 30 milligrams of beta-carotene has been taken once daily for up to seven years with a lack of effect. For HIV support, a large dose of vitamin A (400,000 IU in adults and 50,000 IU in infants) was given to women and infants shortly after birth for two years. In other research, high doses (180 milligrams daily or 600,000 IU) of beta-carotene were given for one month. Lower doses of vitamin A (10,000 IU daily) have also been given to adults in areas of high prevalence of vitamin A. Additionally, 200,000-300,000 IU have been given for 4-8 weeks, but reported a lack of benefit on CD4 counts and viral load. For infant mortality (given to the mother during pregnancy), pregnant women with HIV received iron and folate, either alone or combined with vitamin A (three milligrams of retinol equivalents) daily by mouth from 18-28 weeks of gestation. In other research, pregnant women took 7,000 micrograms of retinol equivalents of vitamin A (as four milligrams of all-trans beta-carotene retinyl palmitate) or 42 milligrams of beta-carotene once weekly by mouth during pregnancy; moreover, vitamin A (5,000 IU-23,300 IU) has been taken with our without 30 milligrams of beta-carotene during pregnancy. Also during 12-24 weeks of gestation, vitamin A (5,000 IU or 10,000 IU) was taken by mouth daily. Doses of 200,000 IU weekly and 200,000 IU at the time of delivery have also been used. For infant mortality (given to mother shortly after childbirth), vitamin A (≤200,000 IU or >200,000 IU) has been given as a single dose or as multiple doses to mothers within six weeks of delivery. Doses consisting of 200,000-400,000 IU of vitamin A or 7.8 milligrams of beta-carotene, alone or in combination with another supplement, have also been taken daily by mouth. For inflammation of the oral mucosa (oral lichen planus), 0.1% tretinoin or 0.05-0.18% isotretinoin two to three times daily for 8-16 weeks, 0.05% retinoic acid four times daily for four weeks, and 0.1% vitamin A twice daily for up to seven days have been applied to the mouth. For liver disease, daily amounts of 5,000 IU of vitamin A have been taken for six months or 10,000 IU for four months. For lung cancer, 20-50 milligrams of beta-carotene was taken by mouth daily or every other day for 5-12 years. For treating lung cancer, 0.5-1 milligram per kilogram of 13-cis-retinoic acid has been given daily for 11 weeks to one year; for the prevention of primary lung cancer, 25,000 IU retinyl palmitate daily in combination with 30 milligrams of beta-carotene or 22.5 milligrams of zinc daily for 13 months to 5.5 years has been used; and for the prevention of secondary lung cancer, 150,000-300,000 IU retinyl palmitate daily or 10-30 milligrams of isotretinoin every other day for one to two years has been used. Additionally, all-trans retinoic acid (ATRA) 20 milligrams per square meter of body surface area has been used injected daily in combination with cisplatin and paclitaxel. For mortality reduction, 1,333-200,000 IU of vitamin A trials has been taken daily or every other day for 28 days to nine years, with a lack of effect on all-cause mortality. For mortality reduction (for the mother shortly after childbirth), vitamin A has been taken during pregnancy at doses ranging from 5,000-10,000 IU daily, about 200,000 IU weekly, and 200,000 IU at the time of delivery. For oral leukoplakia, vitamin A (as retinyl acetate) was given by mouth at doses of 300,000 IU weekly for 12 months, 200,000 IU of vitamin A (form unclear) weekly (0.14 milligrams per kilogram of body weight) daily for six months, or 13-cis-retinoic acid 1-2 milligrams per kilogram of body weight daily for three months. In addition, 0.05-0.18% isotretinoin gel three times daily for four months, 0.05% tretinoin gel four times daily for a mean follow-up of 23 months, or 20 milligrams of acitretin daily have been applied to the mouth. For psoriasis, one milligram per kilogram of retinoids was taken daily (frequency information lacking). Additionally, 10-75 milligrams of acitretin was taken by mouth daily either alone or in combination with psorlen plus ultraviolet A/B (PUVA/PUVB) light, and one milligram per kilogram or 75 milligrams of etretinate was taken by mouth daily for six weeks to 12 months. For radiation therapy side effects, 10,000 IU retinol palmitate was taken daily for 90 days. For retinitis pigmentosa (vision disorder), the National Eye Institute (NEI) recommends that patients with typical forms of retinitis pigmentosa receive 15,000 IU of vitamin A palmitate daily under medical supervision. For skin cancer, 100,000 IU of vitamin A was taken daily by mouth for 18 months; however, there was an overall lack of benefit with vitamin A therapy. For skin damage caused by the sun, 0.02% or higher doses of tretinoin have been applied to sun-damaged skin once daily for a treatment duration of 4-11 months; other retinoids, tazarotene 0.01-0.1% and isotretinoin 0.1%, were also applied to the skin once daily. For tuberculosis, 5,000-200,000 IU has been taken three times before starting tuberculosis therapy with one study having a treatment duration of six months. Children (under 18 years old) Recommended dietary allowances (RDAs) have been established by the U.S. Institute of Medicine of the National Academy of Sciences. The recommendations are as follows: for children 1-3 years old, 300 micrograms (1,000 IU) daily; for children 4-8 years old, 400 micrograms (1,300 IU) daily; and for children 9-13 years old, 600 micrograms (2,000 IU) daily. For pregnant women 14-18 years old, 750 micrograms (2,500 IU) daily is recommended. For lactating women 14-18 years old, 1,200 micrograms (4,000 IU) daily is recommended. The World Health Organization (WHO) has established dosage guidelines for children 6-11 months old to receive 100,000 IU of vitamin A. This increases to 200,000 IU every six months from 12 to 59 months of age. For acute promyelocytic leukemia, 25-45 milligrams of all-trans retinoic acid (ATRA) has been taken daily until complete remission or for up to two years in combination with cancer therapy. For anemia, 3,000 micrograms of vitamin A has been taken by mouth daily for two months. For bronchopulmonary dysplasia in premature infants, 2,000 IU has been taken every other day or 4,000 IU has been taken three times weekly by mouth. For childhood growth promotion, 60 milligrams of vitamin A has been taken in one to six doses separated by 4-6 months, for 12-104 weeks. Other studies administered 2,500 micrograms of vitamin A weekly for one year or as a single large dose of 60,000 micrograms. For cystic fibrosis, the 2002 cystic fibrosis guidelines recommend vitamin A supplements for all children with cystic fibrosis and pancreatic insufficiency, specifically 3,000 micrograms of retinol activity equivalents (RAEs) daily for children over the age of eight years. For infant mortality, the following has been taken: three milligrams by mouth daily from 18 to 28 weeks’ gestation; 7,000 micrograms by mouth once weekly during gestation; 5,000-10,000 IU daily by mouth from 12-24 weeks’ gestation; 200,000 IU weekly, or 200,000 IU at time of delivery; and 200,000-400,000 IU daily by mouth shortly after childbirth. A dose of 2,000 IU has been injected into the muscle of infants every two days for 28 days. Also injected into the muscle, 4,000 IU every two days or 3,750 IU every two days for 16 days has been used. Doses between 1,500 IU and 5,000 IU, by mouth or injected into the muscle of the infant, have been used every other day or three times weekly. Doses from 8,333 IU weekly to 200,000 IU every six months by mouth have been used. In neonates, 5,000 IU per kilogram of vitamin A has been used daily for four weeks or 25,000-50,000 IU of vitamin A (cumulative dose). Within 24-72 hours of delivery, 25,000-400,000 IU of vitamin A divided in one to two oral doses has been taken. Intramuscular injections of vitamin A were given as follows: 2,000 IU every two days for 28 days (14 injections in total), 4,000 IU every two days (duration unclear), 5,000-10,000 IU vitamin A three days weekly, 15,000 IU vitamin A weekly for four weeks, or 3,750 IU every two days for 16 days (eight injections in total). Injections of 1,500-4,000 IU vitamin A every other day or three times weekly for up to four weeks and a lipid emulsion containing 80,000 retinol equivalents per liter of retinyl palmitate for 16 hours plus 1,300-3,300 IU per kilogram of vitamin A daily for two weeks have also been used. For malaria, children aged 6-60 months were given one capsule (or half a capsule if younger than 12 months) of 200,000 IU of vitamin A (in 200 microliters of peanut oil with 10 micrograms of vitamin E as a preservative) every three months for 13 months. For measles, the World Health Organization (WHO) recommends 200,000 IU daily by mouth for two days for children with measles who live in areas of vitamin A deficiency. For infants with measles, the WHO recommends 100,000 IU daily by mouth for two days. For childhood mortality, doses from 8,333 IU weekly to 200,000 IU every six months by mouth have been used. Doses from 10,000 IU weekly for 40 weeks to 206,000 IU once every four months, for up to six doses, have been used. For HIV, a large dose of vitamin A (400,000 IU in adults and 50,000 IU in infants) has been given to women and infants shortly after childbirth for two years. For neuroblastoma (cancer of nerve tissue), 22.5-200 milligrams daily of 13-cis-retinoic acid has been taken daily for up to four years alone or with chemotherapy. For respiratory tract infections, oral doses of vitamin A were as follows: 25,000 IU for a total of three doses, 10,000 IU weekly for a total of 40 doses, 200,000 IU (half dose for infants less than 12 months old) for a total of 2-3 doses at 4-6-month intervals, 206,000 IU (half dose for infants less than 12 months old) for a total of six doses over two years, 200,000 IU (half dose for infants less than 12 months old) for a total of six doses over 23 months, 200,000 IU (half dose for infants less than 12 months old) for a total of three doses over 12 months, 2,500 micrograms weekly for 52 weeks. For tuberculosis, 5,000 IU or 200,000 IU of vitamin A, alone or in combination with zinc, was taken up to twice daily and 5,000 IU or 8,000 IU of vitamin A as part of a multi-supplement regimen was taken daily, weekly, or as a single dose for 2-24 months. For xerophthalmia (dry eye), the World Health Organization (WHO) recommends 200,000 IU daily by mouth immediately on diagnosis, 200,000 IU on the following day, and then 200,000 IU prior to discharge, or if clinical deterioration occurs, or 2-4 weeks later. Infants under 12 months of age and very small and very-low-weight children should be given half the dosage. Safety The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects. Allergies Avoid in individuals with a known sensitivity or allergy to vitamin A or any part of the formulation. Side Effects and Warnings Vitamin A is considered safe when consumed in recommended dietary allowances (RDAs). Adults who eat fortified foods with vitamin A, such as low-fat dairy products and a lot of fruits and vegetables, generally lack the need for supplements or multivitamins that contain vitamin A. Vitamin A may cause bleeding in the lungs, blurry vision, bone pain, breathing difficulty, changes in immune function, chronic inflammation of the liver, cirrhosis (scarring of liver), cough, cracked fingernails, cracked lips, death, decreased thyroid function, depression, diarrhea, feeling of fullness, fever, fluid around heart, hair loss, high cholesterol, increased pressure in the brain, increased risk of HIV transmission (through breastfeeding), increased risk of lung cancer, increased risk of heart disease, increased white blood cells, indigestion, inflammation of the conjunctiva (conjunctivitis), injection site pain, irritability, joint pain, mouth ulcers, muscle pain, psoriasis flare-ups, pain, perisinusoidal fibrosis (in the liver), redness (from skin use), respiratory infection, seizure, skin irritation, sore eyes, steatosis (fatty change), stomach and intestine adverse effects, and suicidal thoughts. Vitamin A toxicity is rare in the general population. Vitamin A toxicity can occur with high amounts of vitamin A taken over short or long periods of time. Consequently, toxicity can be short or long-term. Symptoms of acute (short-term) toxicity include nausea, headache, fatigue, loss of appetite, dizziness, dry skin, desquamation (loss of skin), and cerebral edema (swelling in the brain). Symptoms of chronic (longer-term) toxicity include dry itchy and cracking skin, desquamation, dry lips, scaling anorexia, headache, psychiatric changes, cerebral edema (excess fluid), bone and joint pain, osteoporosis (bone loss), and hip fracture. Severe toxicity can lead to eye damage, high levels of calcium, and liver damage. In children, signs of toxicity include irritability, drowsiness, dizziness, delirium, coma, vomiting, diarrhea, increased pressure in the brain with bulging fontanelles in infants, headache, swelling of the optic (eye) disk, bulging eyeballs, visual disturbances, and skin redness and peeling. People with liver disease and high alcohol intake may be at risk for liver toxicity from vitamin A supplementation. Vitamin A toxicity may lead to intrahepatic cholestasis, where bile cannot flow from the liver into the intestines. Vitamin A may cause low blood pressure. Caution is advised in people with low blood pressure or in those taking drugs or herbs and supplements that lower blood pressure. Use cautiously in combination with bile acid sequestrants, mineral oil, neomycin, or orlistat, due to reduced absorption of vitamin A. Use cautiously in combination with contraceptives taken by mouth, due to increased levels of vitamin A. Use cautiously in combination with alcohol or anticancer agents, due to the potential for increased risk of adverse effects. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Use cautiously in smokers who consume alcohol. Use cautiously in children and infants, or in people with osteoporosis, skin disorders, thyroid disorders, affective disorders, or those taking agents for depression. Avoid taking vitamin A in high doses, due to increased risk of toxicity and death. Avoid in combination with tetracycline antibiotics, agents that are toxic to the liver, or retinoids, due to the increased risk of toxic effects. Avoid in people with poor fat absorption, intestinal infections, severe protein energy malnutrition, liver disease, or type V hyperlipoproteinemia (a genetic disorder). High-dose vitamin A and beta-carotene should be avoided in patients at high risk of lung cancer. Vitamin A may increase the risk of bleeding. Avoid use when taking agents that affect bleeding and clotting. Avoid in individuals with a known sensitivity or allergy to vitamin A or any part of the formulation. Pregnancy and Breastfeeding Vitamin A should only be used within the recommended dietary allowance, because vitamin A excess, as well as deficiency, has been associated with birth defects. Excessive doses of vitamin A have been associated with central nervous system malformations. Vitamin A is excreted in human breast milk. The benefits or dangers to nursing infants are unclear. Tretinoin that is applied to the skin is likely low risk for breastfeeding infants given its poor absorption; however, due to a lack of evidence, caution should be taken to prevent direct skin contact to the nursing infant and only water soluble cream or gel products should be applied. Interactions Interactions with Drugs Vitamin A may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®). Vitamin A may interfere with the way the body processes certain drugs using the liver’s cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased or decreased in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions. Vitamin A may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure. Vitamin A may also interact with agents for depression, agents for diarrhea, agents for lowering cholesterol, agents for the stomach and for intestine disorders, agents for weight loss, agents for worm infections, agents that affect the nervous system, agents that affect the liver, alcohol, antibiotics, anticancer agents, antifungals, antimalarials, antivirals, birth control agents taken by mouth, folate agents, iron salts, mineral oil, nicotine, orlistat, osteoporosis agents (for decreased bone density), phytonadione (vitamin K), retinoids, skin disorder agents, thyroid agents, vaccines, and valproic acid. Interactions with Herbs and Dietary Supplements Vitamin A may increase the risk of bleeding when taken with herbs or supplements that increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases. Vitamin A may interfere with the way the body processes certain herbs or supplements using the liver’s cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too high or too low in the blood. It may also alter the effects that other herbs or supplements possibly have on the cytochrome P450 system. Vitamin A may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure. Vitamin A may also interact with antibacterials, anticancer herbs and supplements, antifungals, antimalarials, antioxidants, antivirals, apple pectin, carob, carrageenan, cholesterol-lowering herbs and supplements, fat-soluble vitamins, fiber, folic acid, guar, herbs and supplements for birth control, for bone loss, for depression, for diarrhea, for obesity, for stomach and intestine disorders, and for worm infections, herbs and supplements that affect the nervous system, herbs and supplements that affect the thyroid, herbs and supplements that affect the liver, iron, microcrystalline cellulose, multiple micronutrient supplements, plant stanols and sterols, tobacco, vitamin E, vitamin K, wheat bran, and zinc.