Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-trans retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system. Certain carotenoids, such as beta-carotene alpha-carotene and beta-cryptoxanthin, are dietary precursors of vitamin A. Collectively, these substances are called provitamin A. (See Beta-Carotene). The term retinoids refers to retinol and its metabolites, such as retinoic acid, as well as to synthetic analogues that are structurally similar to retinol but may not have the same biological activities as retinol.
Vitamin A deficiency can result in night blindness (defective vision at low illumination), xerosis of the conjunctiva and cornea (destruction of the cornea secondary to vitamin A deficiency or xerophthalmia is a major cause of blindness in children), keratinization of the lung, gastrointestinal tract and urinary tract epithelia, growth retardation, follicular hyperkeratosis of the skin, increased susceptibility to infections and death. Children are particularly susceptible to the effects of vitamin A deficiency. Deficiency of the vitamin is a serious public health issue in developing countries.
Vitamin A deficiency was probably the first nutritional deficiency to be recognized. The ancient Egyptians and Greeks apparently treated the corneal changes due to deficiency of the vitamin and night blindness by the topical application and the feeding of liver, a rich source of vitamin A. In addition to liver, other rich sources of vitamin A are fish liver oils (e.g., cod liver oil), egg yolks, butter and cream. Vitamin A occurs naturally in the form of fatty acid esters, such as vitamin A palmitate (retinyl palmitate).
Vitamin A deficiency occurs under certain conditions. These include inadequate dietary intake of vitamin A or provitamin A, malabsorption syndromes (cystic fibrosis, Whipple's disease, Crohn's disease, ulcerative colitis, short bowel syndrome), pancreatic disease and chronic liver disease (e.g., cirrhosis).
The effects of vitamin A are mediated by two different mechanisms. The eye illustrates both of these mechanisms. Vitamin A (all-trans retinol) is converted in the retina to the 11-cis-isomer of retinaldehyde or 11-cis-retinal. 11-cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to 11-cis-retinol in the dark, and then oxidized to 11-cis-retinal. 11-cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to resynthesize 11-cis retinal rapidly. This is a consequence of vitamin A deficiency. Vitamin A deficiency results in the depletion of the vitamin A storage pool (retinyl ester) in the retinal pigment epithelial cells.
The normal differentiation of the cells of the cornea and conjunctiva is dependent on another metabolite of vitamin A, retinoic acid. Retinoic acid acts as a hormone and is involved in signal transduction. Retinoic acid signaling and signaling by other retinoids are mediated by two classes of nuclear receptors, retinoic acid receptors (RAR-alpha, -beta and -gamma) and retinoid X receptors (RXR-alpha, -beta and -gamma). The RARs and RXRs belong to the superfamily of nuclear hormone receptors. Members of this family, which, in addition to retinoic acid, include receptors for small hydrophobic hormones, such as steroids, the biologically active form of vitamin D, thyroid hormones and metabolites of long-chain fatty acids, associate with DNA response elements in the promoter region of target genes and act either to activate or repress transcription. The response elements to which retinoic acid and other retinoids bind to are called retinoid response elements. The role of vitamin A in epithelial differentiation, as well as in other physiological processes, is thought to be mediated via retinoic acid's hormonal activity.
High-dose vitamin A has been used in the management of various skin disorders, including acne; Darier's disease or keratosis follicularis, an autosomal dominant disorder of keratinization; pityriasis rubra pilaris, an abnormality of follicular keratinization; Kyrle's disease, a focal derangement of orientation of keratinization and xerosis. None of the above uses are FDA approved. FDA-approved retinoids, include tretinoin (all-trans-retinoic acid), which is used topically for acne vulgaris; isotretinoin (13-cis-retinoic acid), for cystic acne; etretinate, a synthetic analog of retinoic acid ethyl ester, for psoriasis; and acitretin, a metabolite of etretinate, also for psoriasis. FDA-approved retinoids used for the treatment of malignancies, include alitretinoin (9-cis-retinoic acid), a topical treatment for Kaposi's sarcoma; all-trans-retinoic acid, for acute promyelocytic leukemia; and bexarotene, for refractory cutaneous T-cell lymphoma.
The parent compound of the vitamin A family is all-trans-retinol. It is also the most abundant dietary form of vitamin A. All-trans-retinol occurs naturally in the form of fatty acid esters, such as vitamin A palmitate (retinyl palmitate). Vitamin A palmitate and vitamin A acetate (retinyl acetate) are the principal forms used as nutritional supplements. All-trans-retinol, as is the case of all forms of vitamin A, is a derivative of beta-ionone. All-trans-retinol is also known as retinol, vitamin A1, anti-infective vitamin, vitamin A alcohol and (all-E)-3, 7-dimethyl-9- (2, 6, 6-trimethyl-1-cyclohexen-1-y1)-2, 4, 6, 8-nonatetraen-1-o1. Its molecular formula is C20H30O and its molecular weight is 286.46 daltons. Its structural formula is:
Other naturally occurring forms of vitamin A, include retinal (retinaldehyde, retinene, vitamin A1 aldehyhde), retinoic acid (vitamin A1 acid), retinoyl-beta-glucuronide (vitamin A1 beta-glucuronide), retinyl phosphate (vitamin A1 phosphate), 3-dehydroretinol (vitamin A2), 11-cis-retinal (11-cis-retinaldehyde, 11-cis or neo b vitamin A1 aldehyde), 5, 6-epoxyretinol (5, 6-epoxy vitamin A1 alcohol), anhydroretinol (anhydro vitamin A1) and 4-ketoretinol (4-keto-vitamin A1 alcohol). Except for all-trans-retinol, retinyl palmitate and retinyl acetate, all the other above-mentioned forms are minor dietary components.
Amounts of vitamin A are expressed in four ways: international units (IU), United States Pharmacopeia (USP) units, micrograms and retinol equivalents. One IU is equal to one USP unit. One IU of vitamin A activity is defined as either equal to 0.30 micrograms of all-trans retinol or to 0.60 micrograms of the provitamin A, all-trans-beta-carotene. One retinol equivalent (RE) is defined as one microgram of all-trans retinol, six micrograms of all-trans-beta-carotene or 12 micrograms of other provitamin A carotenoids.Get Pure Matters all-natural, pure Vitamin A.
Actions & Pharmacology
Vitamin A may prevent loss of vision or restore lost vision. Vitamin A may have anticarcinogenic, immunomodulatory and antioxidant activities.
Mechanism of Action
Vitamin A deficiency can result in night blindness and blindness due to the destruction of the cornea (xerophthalmia). The ability of vitamin A to prevent these two visual problems and its mechanism of action in doing so is well known (see Description). There are a couple of recent reports that suggest vitamin A may affect some visual problems in those who are not vitamin A-deficient. Sorsby's fundus dystrophy (SFD) is an autosomal dominant retinal degeneration disorder which, among other things, can result in night blindness. SFD, both clinically and histopathologically, shares similarities with age-related macular degeneration, the most common cause of loss of vision in the elderly. In an SFD family, it was found that vitamin A at 50,000 IU daily resolved night blindness within a week in those members of the family who were at early stages of the disease. The mechanism of this effect is not clear. The researchers hypothesized that the abnormally thickened Bruch's membrane, with its lipid deposits, acts as a barrier to the diffusion of vitamin A presented from the choroidal vasculature, essentially causing vitamin A deficiency in the retina. According to this hypothesis, large doses of vitamin A over-ride the reduced transport efficiency of retinol across the defective Bruch's extracellular matrix. Direct or indirect effects of retinol on retinal pigment epithelial (RPE) cells are other possibilities. Vitamin A is known to modulate RPE cellular function and behavior. In another study, an oral retinoid was found to restore visual pigment and function in a mouse model of childhood blindness. Leber's congenital amaurosis (LCA) is an autosomal recessive mitochondrial disease which results in retinal degeneration. It is a rare variant of the more common disease, retinitis pigmentosum. Researchers found that administration of the vitamin A form 9-cis-retinal to the mice led to signs of visual improvement. The researchers hypothesized that 9-cis-retinal bypassed the biochemical block in the retina caused by the disease. Human studies are needed. It must be noted, however, that high doses of vitamin A have the potential for serious side effects.
Vitamin A and retinoids have been found to inhibit tumor development, especially those of epithelial origin, in a variety of in vitro studies. All-trans-retinol has been demonstrated to suppress the malignant behavior of cultured cells transformed by radiation, chemicals or viruses, to delay the development of transplanted tumors and to prevent malignancy in animals exposed to various potent carcinogens. It is thought that the anticarcinogenic effect of preformed vitamin A (all-trans-retinol) in these cases are mediated by its conversion to retinoic acid. Retinoic acid, via its binding to nuclear receptors (retinoic acid receptors, retinoid X receptors), may induce cell differentiation, inhibit proliferation and/or induce apoptosis. Many of these results were obtained using doses of all-trans-retinol that were very high and that would be too toxic for general, preventive use. Further, it is unclear whether sufficient conversion of all-trans-retinol to retinoic acid occurs to make a significant anticarcinogenic impact. A recent two-year study (EUROSCAN) of high-dose retinyl palmitate showed no benefit—in terms of survival, event-free survival, or secondary primary tumors—for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.
Some retinoids, however, have shown anticancer effects in certain situations. All-trans-retinoic acid is an approved drug for the treatment of acute promyelocytic leukemia (APL). The mechanism of action of all-trans-retinoic acid in the treatment of APL is not fully understood. Those with APL possess an abnormal gene for retinoic acid receptor-alpha (RAR-alpha). Treatment with all-trans-retinoic acid induces expression of the remaining normal RAR-alpha allele, which may rebalance the receptor system toward normal differentiation. Bexarotene is a synthetic retinoid analogue which is approved for the treatment of cutaneous T-cell lymphoma. The mechanism of action of bexarotene is unknown. It is known to activate retinoid X receptors (RXR), which pair with other cellular receptors to control the expression of genes involved in cellular differentiation and growth. The use of retinoids in the treatment of cancer is known as differentiation therapy.
Vitamin A deficiency results in decreased resistance to infection. Vitamin A deficiency affects both cell-mediated and antibody-mediated immune responses. Nonspecific immune responses involving neutrophils, macrophages and natural killer cells, are also affected by vitamin A deficiency. It is thought that vitamin A's participation in the immune response is via signal transduction pathways which are necessary for the normal functioning of the immune system. Retinol may also stimulate the immune response in animals and humans who are not vitamin A deficient. High doses of retinyl palmitate have been found to stimulate the nonspecific immune system in animals. Retinol and retinoic acid have also been found to enhance the antibody response to specific antigens, again, in animals. In surgery patients treated with high doses of vitamin A for seven days after surgery, lymphocyte proliferation did not differ from the control group after one day, but was significantly greater after seven days. The mechanism of action of the possible immunomodulatory effect of vitamin A is not well understood. Further, the studies of immunomodulation in animals that were not vitamin A-deficient used vitamin A doses that would be toxic in humans.
Vitamin A deficiency has been found to cause oxidative damage to liver mitochondria in rats. In these animals, a deficit of Vitamin A produced an increase in oxidized glutathione, malondialdehyde, 8-oxo-deoxyguanosine, a drop in the mitochondrial membrane potential and an 80% decrease in the reduced glutathione to oxidized glutathione ratio. Vitamin A has also been found to protect against lipid peroxidation induced by doxorubicin in heart and brain membrane lipids and to inhibit chemiluminescence and lipid peroxidation in isolated rat liver microsomes and mitochondria. The antioxidant mechanism of vitamin A is thought to be due, in part, to the hydrophobic chain of polyene units, which can quench singlet oxygen, neutralize thiyl radicals and stabilize and combine with peroxyl radicals.
Preformed vitamin A is present in food in the form of retinyl esters. The principal nutritional supplement forms of preformed vitamin A are retinyl palmitate and retinyl acetate. Retinyl palmitate is also used in food fortification. Preformed vitamin A is efficiently absorbed from the small intestine. The efficiency of absorption ranges from 60%-90%. Vitamin A absorption requires bile salts, pancreatic enzymes and dietary fat. Vitamin A is delivered to the enterocytes in the form of micelles. Prior to its absorption, the retinyl esters are hydrolyzed by a pancreatic hydrolase. Long-chain retinyl esters, such as retinyl palmitate, appear to be hydrolyzed by a hydrolyase which is a component of the brush border. Within the enterocytes, all-trans-retinol is re-esterified to retinyl esters and the retinyl esters are secreted by the enterocytes into the lymphatics in the form of chylomicrons.
The chylomicrons enter the circulation via the thoracic duct. Chylomicrons undergo metabolism in the circulation via lipoprotein lipase to form chylomicron remnants. Most of the retinyl esters in chylomicron remnants are rapidly taken up into liver parenchymal cells. Within the liver parenchymal cells, retinyl esters are again hydrolyzed to all-trans-retinol and fatty acids. All-trans-retinol may be stored in the liver as retinyl esters or may be transported in the circulation bound to serum retinol binding protein (RBP). RBP delivers retinol to the various tissues. Approximately 50%-85% of the total body vitamin A content is stored in the liver. Greater than 95% of serum retinol is present in its unesterified form.
Serum retinol binding (RBP) protein is the principal carrier of all-trans-retinol, which comprises over 90% of serum vitamin A. RBP is found in serum in association with a cotransport protein called transthyretin or prealbumin. The mechanism of the transport of retinol into target cells is not known. Within cells, retinol and its metabolites are bound to retinoid-binding proteins in the cytosol and nucleus. The cytosolic retinoid-binding proteins are: cellular retinol-binding protein I (CRBP-I), cellular retinol-binding protein II (CRBP-II), cellular retinoic acid-binding protein I (CRABP-I) and cellular retinoic acid-binding protein II (CRABP-II). The nuclear retinoid-binding proteins are: retinoic acid receptor-alpha (RAR-alpha), retinoic acid receptor-beta (RAR-beta), retinoic acid receptor-gamma (RAR-gamma), retinoid X receptor-alpha (RXR-alpha), retinoid X receptor-beta (RXR-beta) and retinoid X receptor-gamma (RXR-gamma). The cytosolic retinoid-binding proteins limit the amounts of unbound or free retinoids and channel them to specific enzymes responsible for their metabolism. The nuclear retinoid-binding proteins bind retinoids and regulate the activities of retinoid-responsive genes.
All-trans retinol is oxidized to retinal via retinol dehydrogenase: retinal is metabolized to retinoic acid via retinal dehydrogenase. All-trans-retinol is delivered to the cornea via the tears and by diffusion through eye tissue. Retinol and retinoic acid form a number of oxidized metabolites. The metabolites of retinol and retinoic acid undergo glucuronidation, glucosylation and amino acylation and are excreted mainly via the biliary route. Some excretion of retinol and its metabolites occurs via the kidneys.Get Pure Matters all-natural, pure Vitamin A.
Indications & Usage
A major role has emerged for vitamin A in the treatment of malnourished children, principally in developing countries. It is credited with significantly reducing mortality and the incidence of blindness, diarrhea, measles and some other infections in these populations. Vitamin A appears to have many positive effects in the immune system and may have some anti-cancer effects. It can help with some skin conditions and may be useful in some with Sorsby's fundus dystrophy. There is emerging evidence that vitamin A plays crucial roles in embryonic development, and some believe it will eventually be used to prevent teratogenesis under some circumstances. Pregnant women, however, should not use doses of vitamin A greater than the U.S. RDA (5,000 IU/day) without a physician's recommendation and supervision.Get Pure Matters all-natural, pure Vitamin A.
Acute toxicity in infants or children can occur with a single dose of 25,000 IU per kilogram of body weight. Vomiting, increased intracranial pressure and death may occur. A dose of 2,000,000 IU or greater in adults, can cause a similar clinical picture. Some Arctic explorers have ingested several million units of vitamin A from eating polar bear or seal liver, two of the richest sources of vitamin A. The Arctic explorers developed irritability, drowsiness, headache and vomiting. There are few reports of fatalities with such high doses of vitamin A.Get Pure Matters all-natural, pure Vitamin A.
The two principal forms of vitamin A supplements are retinyl acetate and retinyl palmitate. Multivitamin preparations contain vitamin A in one of these forms, a combination of vitamin A and beta-carotene (provitamin A) or beta-carotene alone. Rarely are doses higher than 5,000 IU of vitamin A exceeded in these formulas. Supplemental doses of vitamin A greater than 10,000 IU daily are not recommended. Many take beta-carotene for vitamin A supplementation (see Beta-Carotene). Vitamin A is also available in the form of cod liver oil.
|Dietary Reference Intake (DRI) values for Vitamin A|
|DRI values—microgram Retinol Activity Equivalent (RAE)/day|
|Infants||Adequate Intake (AI)|
|0-6 months||400 (1,333 IU)|
|7-12 months||500 (1,667 IU)|
|Recommended Daily Allowance Children||(RDA)|
|1-3 years||300 (1,000 IU)|
|4-8 years||400 (1,333 IU)|
|9-13 years||600 (2,000 IU)|
|14-18 years||900 (3,000 IU)|
|9-13 years||600 (2,000 IU)|
|14-18 years||700 (2,333 IU)|
|19-30 years||900 (3,000 IU)|
|31-50 years||900 (3,000 IU)|
|51-70 years||900 (3,000 IU)|
|Older than 70 years||900 (3,000 IU)|
|19-30 years||700 (2,333 IU)|
|31-50 years||700 (2,333 IU)|
|51-70 years||700 (2,333 IU)|
|Older than 70 years||700 (2,333 IU)|
|14-18 years||750 (2,500 IU)|
|19-30 years||770 (2,567 IU)|
|31-50 years||770 (2,567 IU)|
|14-18 years||1,200 (4,000 IU)|
|19-30 years||1,300 (4,333 IU)|
|31-50 years||1,300 (4,333 IU)|
The following summarizes the Tolerable Upper Intake Level (UL) for various age groups and conditions:
|1-3 years||600 (2,000 IU)|
|4-8 years||600 (2,000 IU)|
|9-13 years||1,700 (5,660 IU)|
|14-18 years||2,800 (9,300 IU)|
|19 years and older||3,000 (10,000 IU)|
|14-18 years||2,800 (9,300 IU)|
|19 years and older||3,000 (10,000 IU)|
|14-18 years||2,800 (9,300 IU)|
|19 years and older||3,000 (10,000 IU)|
The DV (Daily Value) for vitamin A, which is used for determining percentage of nutrient daily values on nutritional supplement and food labels, is 5,000 IU (International Units). The basis for the DV for vitamin A is the U.S. RDA.Get Pure Matters all-natural, pure Vitamin A.
LiteratureAcott TS, Weleber RG. Vitamin A megatherapy for retinal abnormalities. Nature Med. 1995;1:884-885.Barber T, BorrÁs E, Torres L, et al. Vitamin A deficiency causes oxidative damage to liver mitochondria in rats. Free Rad Biol Med. 2000;29:1-7.Barreto ML, Santos LMP, Assis AMO, et al. Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil. Lancet. 1994;344:228-231.Bates CJ. Vitamin A. Lancet. 1995;345:31-35.Benn CS, Aaby P, Balé C, et al. Randomized trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, West Africa. Lancet. 1997;350:101-105.Chiang M-Y, Misner D, Kempermann G, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron. 1998;21:1353-1361.Collins MD, Mao GE. Teratology of retinoids. Annu Rev Pharmacol Toxicol. 1999;39:399-430.Futoryan T, Gilchrest BA. Retinoids and the skin. Nutr Rev. 1994;52:299-310.Gilchrest B. Anti-sunshine vitamin A. Nature Med. 1999;5:376-377.Hadi H, Stoltzfus RJ, Dibley MJ, et al. Vitamin A supplementation selectively improves the linear growth of Indonesian preschool children: results from a randomized controlled trial. Am J Clin Nutr. 2000;71:507-513.Humphrey JH, Rice AL. Vitamin A supplementation of young infants. Lancet. 2000;356:422-424.Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.Jacobson SG, Cideciyan AV, Regunath G, et al. Night blindness in Sorsby's fundus dystrophy reversed by vitamin A. Nature Gen. 1995;11:27-32.Kowalski TE, Falestiny M, Furth E, Malet PF. Vitamin A hepatotoxicity: a cautionary note regarding 25,000 IU supplements. Am J Med. 1994;97:523-528.Lee M-O, Han S-Y, Jiang S, et al. Differential effects of retinoic acid on growth and apoptosis in human colon cancer cell lines associated with the induction of retinoic acid receptor beta. Biochem Pharmacol. 2000;59:485-496.Ribaya-Mercado, JD, Blumberg JB. Vitamin A: is it a risk factor for osteoporosis and bone fracture? Nutr Rev. 2007;65(10):425-438.Ross AC. Vitamin A and retinoids. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams and Wilkins;1999:305-327.Ross AC, Stephensen CB. Vitamin A and retinoids in antiviral responses. FASEB J. 1996;10:979-985.Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. N Engl J Med. 1995;333:1369-1373.Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr. 2000;71:878-884.Sohlenius-Sternbeck A-K, Appelkvist E-L, De Pierre JW. Effects of vitamin A deficiency on selected xenobiotic-metabolizing enzymes and defenses against oxidative stress in mouse liver. Biochem Pharmacol. 2000;59:377-383.Underwood BA, Arthur P. The contribution of vitamin A to public health. FASEB J. 1996;10:1040-1048.Van Hooser JP, Aleman TS, He Y-G, et al. Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness. Proc Natl Acad Sci USA. 2000;97:8623-8628.Varani J, Warner RL, Gharaee-Kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000;114:480-486.Wang Z, Boudjelal M, Kang S, et al. Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment. Nature Med. 1999;5:418-422.West KP Jr, Pokhrel RP, Katz J, et al. Efficacy of vitamin A in reducing preschool child mortality in Nepal. Lancet. 1991;338:67-71.Wolf G. A history of vitamin A and retinoids. FASEB J. 1996; 10:1102-1107.Wolf G. A regulatory pathway of thermogenesis in brown fat through retinoic acid. Nutr Rev. 1995;53:230-231.Wolf G. Vitamin A functions in the regulation of the dopaminergic system in the brain and pituitary gland. Nutr Rev. 1998; 56:354-358. Get Pure Matters all-natural, pure Vitamin A.
Research & Summary
Several large, well-controlled, double-blind intervention trials have shown that intermittent high-dose vitamin A supplementation in malnourished children can significantly reduce mortality and the incidence of blindness, diarrhea, measles and some other infections. In one of these trials, there was a significant 27% relative reduction in mortality from all causes in children who received vitamin A supplementation. In another study, this one involving 11,200 children in Indonesia, there was a 30% lower mortality in supplemented children. Six of eight such intervention studies have shown significant reductions in mortality.
Other studies have shown significant reduction in morbidity in similar populations supplemented with vitamin A. Significant reductions in xerophthalmia, blindness, measles, diarrhea and some parasitic infections have been reported. Less dramatic effects have been seen in respiratory infections. The World Health Organization estimates that there are 250 million preschool-age children worldwide whose health may be compromised by vitamin A deficiency. For some years, WHO and some other health organizations have recommended administering large doses of vitamin A to at-risk children at the time they are vaccinated for measles. This practice caused concern when one study suggested that the vitamin A dose was interfering with seroconversion to live measles vaccine in infants with maternal antibodies. A more recent study, however, has refuted this finding to the satisfaction of many. The researchers concluded that ""there is no indication that simultaneous administration of measles vaccine and vitamin A supplements has a negative effect on measles immunity.''
Vitamin A's effects on immunity generally appear to be broad. It was demonstrated some years ago that high-dose vitamin A can significantly protect against some of the immune-depressing effects of radiation and cancer chemotherapy. Animal and in vitro work, as well as some human work, has shown that vitamin A can protect immune function by helping to maintain the integrity of epithelial barriers to infection and by activating phagocytes and cytotoxic T-cells, among other activities.
There is some evidence that vitamin A can stimulate and otherwise favorably affect the immune system even in the absence of frank or marginal vitamin A deficiency. Such effects have been demonstrated in a number of animal models.
An in vitro experiment showed that a form of vitamin A found in breast milk inhibits herpes simplex virus-1. And vitamin A, administered to surgical patients in large daily doses (90 to 135 milligrams) for seven days, significantly increased lymphocyte proliferation. Research on the immune-modulating effects of vitamin A continues. Many in vitro and some animal studies have shown that vitamin A can inhibit malignant activity in various types of cells adversely affected by radiation, chemicals and viruses. The vitamin variously delayed or prevented malignancy in animals exposed to several different carcinogens. Drug derivatives of vitamin A have demonstrated efficacy against some cancers and pre-cancerous lesions, including oral leucoplakia, myelodisplastic syndrome, cutaneous T-cell lymphoma and cervical cancer. Retinoids have been shown to help regulate the expression of some proto-oncogenes and protein growth factors. And retinoic acid has demonstrated an ability to inhibit proliferation of some tumor cells and to promote differentiation of some other cancer cells in vitro.
On the other hand, vitamin A, in combination with beta-carotene, showed no anti-cancer efficacy in an aborted intervention study of smokers, former smokers and workers exposed to asbestos. There was a statistically non-significant increase in incidence of lung cancer and mortality in the treated group. (See Beta-Carotene.)
Vitamin A and its drug derivatives have been used with significant success in the treatment of several skin disorders, including cystic acne, acne vulgaris, psoriasis and photoaged skin. High-dose vitamin A and theses drugs require careful medical supervision and must not be used during pregnancy, owing to risk of birth defects.
One study has shown that high-dose vitamin A (50,000 IU per day) significantly reversed night blindness in some with Sorsby's fundus dystrophy, a rare autosomal retinal degeneration disorder that is clinically similar to age-related macular degeneration. Lower doses (5,000 IU daily) had no effect, but it was suggested that lower doses begun early in disease progression might be helpful. Testing with intermediate doses was also proposed.
Recently, research has suggested that vitamin A might be helpful in preventing some birth defects—surprising to some, since high-dose vitamin A supplementation is itself associated with risk of birth defects. But so is vitamin A deficiency. Current research shows that retinoic acid signaling is crucial for proper development of the early embryonic mesoderm. There are further suggestions that impaired retinoid signaling could have negative effects not only on the embryo but later in life, as well, in terms of neurologic and behavioral development and function. Even schizophrenia, some researchers believe, may be promoted by retinoid defects. Obviously, much more research will be required before any possible strategies for safely and effectively utilizing vitamin A for the prevention of birth defects emerge.Get Pure Matters all-natural, pure Vitamin A.
Contraindications, Precautions & Adverse Reactions
Doses of vitamin A above 5,000 IU are contraindicated in pregnant women.
Vitamin A is contraindicated in those hypersensitive to any component of a vitamin A-containing product.
Vitamin A is contraindicated in those with hypervitaminosis A.
The use of vitamin A for the treatment of vitamin A deficiency requires medical supervision.
The use of vitamin A or any retinoid for the treatment of any medical condition must be prescribed and supervised by a physician.
Nursing mothers should avoid doses of vitamin A great than the U.S. RDA (5,000 IU daily), unless prescribed by a physician.
Supplemental vitamin A may add to the toxicity of retinoids or retinoid analogues which are used pharmaceutically. These include acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin. Those taking any of these drugs should avoid the use of supplemental vitamin A.
Too little or too much vitamin A may increase the risk of osteoporosis. Further research into the relationship between vitamin A and the risk of osteoporosis is needed and warranted. For now, doses higher than the DV or U.S. RDA (5,000 IU) should not be used except if medically indicated and prescribed and monitored by a physician.
High intakes of vitamin A may cause acute or chronic toxicity. (see overdosage for acute toxicity). Symptoms and signs of chronic toxicity include dry rough skin, cracked lips, sparse coarse hair and alopecia of the eyebrows. These are early signs. Late symptoms and signs include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal hypertension, hepatic fibrosis and cirrhosis. There are a few reports of death secondary to liver failure.
Supplemental doses of 10,000 IU of vitamin A daily or greater have been reported to increase the risk of birth defects when used by pregnant women.
Subjects in the EUROSCAN study were given 300,000 IU/day of vitamin A for one year followed by 150,000 IU/day for the second year. Typical side effects were mucocutaneous ones (dryness, desquamation, itching, bleeding and hair loss).
Hepatotoxicity has been reported in one patient who took 25,000 IU/day of vitamin A over a six-year period.Get Pure Matters all-natural, pure Vitamin A.
Cholestyramine: Concomitant intake of cholestyramine and vitamin A may reduce the absorption of vitamin A.
Colestipol: Concomitant intake of colestipol and vitamin A may reduce the absorption of vitamin A.
Mineral Oil: Concomitant intake of mineral oil and vitamin A may reduce the absorption of vitamin A.
Oral Contraceptives: Oral contraceptives may increase serum retinol.
Orlistat: Orlistat may decrease the absorption of vitamin A.
Retinoid Drugs (acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin): Supplemental vitamin A may add to the toxicity of these drugs (see Precautions).
Vitamin K: Intake of large doses of vitamin A may decrease the absorption of vitamin K.
Olestra: The fat substitute olestra inhibits the absorption of vitamin A as well as the other fat-soluble vitamins D, E and K. These vitamins are added to olestra to compensate for this. Olestra contains 170 IU of vitamin A per gram (51 retinol equivalents per gram).Get Pure Matters all-natural, pure Vitamin A.